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2 5-aminolevulinate
porphobilinogen + 2 H2O
5-aminolevulinate
porphobilinogen + H2O
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
additional information
?
-
2 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinate
?
-
-
-
-
?
5-aminolevulinate
?
-
induction by 17beta-estradiol of 5-aminolevulinate
-
-
?
5-aminolevulinate
?
-
-
-
-
?
5-aminolevulinate
?
-
during erythropoiesis in chordates the enzyme functions as a part of the heme synthesizing machinery
-
-
?
5-aminolevulinate
?
-
second enzyme in the heme biosynthetic pathway
-
-
?
5-aminolevulinate
?
-
the second and rate-limiting enzyme of the heme-biosynthetic pathway
-
-
?
5-aminolevulinate
?
-
enzyme catalyzes the first common step in tetrapyrrole biosynthesis
-
-
?
5-aminolevulinate
?
enzyme catalyzes the first common step in tetrapyrrole biosynthesis
-
-
?
5-aminolevulinate
porphobilinogen + H2O
-
-
-
-
?
5-aminolevulinate
porphobilinogen + H2O
-
-
-
-
?
5-aminolevulinate
porphobilinogen + H2O
-
-
-
-
?
5-aminolevulinate
porphobilinogen + H2O
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
(3R)-5-aminolevulinate shows a significantly larger isotope effect than (3S)-5-aminolevulinate
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
(3R)-5-aminolevulinate shows a significantly larger isotope effect than (3S)-5-aminolevulinate
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
essential step in tetrapyrrole biosynthesis
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
the enzyme catalyzes the first common step in the biosynthesis of tetrapyrroles
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
the enzyme functions in the first common step in tetrapyrrole biosynthesis
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
incubations of erythrocytes for 24 h with glucose result in an increase of delta-ALA-D activity. Incubations of erythrocytes with 100 to 200 mM glucose for 48 h inhibit delta-ALA-D activity
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
the role of the enzyme may be confined to heme synthesis in the apicoplast that may not account for the total de novo heme biosynthesis in the parasite
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
porphobilinogen synthase catalyzes the first committed step of the tetrapyrrole biosynthesis pathway
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
enzymatic mechanism starts with formation of a C-C bond, linking C3 of the A-side 5-aminolevulinic acid to C4 of the P-side 5-aminolevulinic acid through an aldole addition
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
the enzyme catalyzes the third step of tetrapyrrole synthesis leading to the formation of heme and chlorophylls in plant tissues. In the light, both 5-aminolevulinate dehydratase activity, and protein level increases 3-4 times compared to the dark-control level. However, no change in the amount of related mRNA is observed. The apparent stability of the mRNA can be due to the abundant expression of a housekeeping gene, which shadows a related gene expressed in the light
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
the enzyme plays a rate-limiting role in heme biosynthesis of saccharomyces cerevisiae
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
-
-
-
-
?
additional information
?
-
-
the enzyme has a dual role: 1. as 5-aminolevulinate dehydatase, the second enzyme in the pathway of heme synthesis, 2. as CF-2 proteasome inhibitor
-
-
?
additional information
?
-
-
direct assay method development with incubation of erythrocyte lysate with the natural substrate, 5-aminolevulinate, followed by quantitative in situ conversion of porphobilinogen to its butyramide and mass spectrometric determination, overview. Using a carbonate buffer rather than phosphate causes nearly a 90% drop in activity and addition of zinc results in a further decrease by up to 35%
-
-
?
additional information
?
-
-
the enzyme stimulates renaturation of luciferase by hsp 70, a member of the heat shock protein 70kDa-family, up to 10fold
-
-
?
additional information
?
-
-
the enzyme stimulates renaturation of luciferase by hsp 70 up to 10fold
-
-
?
additional information
?
-
-
early enzyme of the tetrapyrrole biosynthesis pathway
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ca2+
-
about 80% reactivation of the demetalled protein
Cu2+
-
inhibits enzymatic activity. High molecular weight fraction as well as metallothionein are involved in the detoxification of harmful heavy metals
Cd2+
-
can restore activity of the apoenzyme
Cd2+
-
inhibition at low concentration of substrate and stimulation at high levels of substrate
Cd2+
-
inhibits enzymatic activity. High molecular weight fraction as well as metallothionein are involved in the detoxification of harmful heavy metals
Co2+
-
activates
Co2+
-
about 50% reactivation of the demetalled protein
Co2+
-
partially restores activity after inhibition with EDTA
Co2+
-
about 70% reactivation of the demetalled protein
Fe2+
-
about 70% reactivation of the demetalled protein
Fe2+
-
partially restores enzyme after inactivation of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedisulfonate
K+
-
required
K+
-
activates up to 3 mM
K+
-
stimulates, between pH 6.5 and 7.0, K+ is as stimulatory as Mg2+ and the stimulation is almost 2fold
Mg2+
-
enzyme utilizes a catalytic MgA present at a stoichiometry of 4/octamer, an allosteric MgC present at a stoichiometry of 8/octamer and a monovalent metal ion, K+
Mg2+
-
4 Zn at metal binding site A , 4 Zn at metal binding site B and 8 Mg at metal binding site C are required for full activity per homooctamer
Mg2+
-
Mg(II) causes a twofold stimulation of the Zn(II)-induced activity
Mg2+
-
can not activate the apoenzyme alone, but is able to substitute for the second molar equivalent of bound Zn2+ leading to a further 4fold stimulation
Mg2+
chimeric proteins are constructed that contain the aspartate-rich sequences of the pea enzyme or the enzyme from Pseudomonas aeruginosa in place of the naturally occuring cysteine-rich sequence of the human enzyme. The chimeric enzymes are substantially activated by both magnesium and potassium, but not by zinc
Mg2+
-
4 Zn at metal binding site A and 8 Mg at metal binding site C are required for full activity per homooctamer
Mg2+
-
essentail cofactor, allosteric Mg(II) binds with a Kd of 2.5 mM, 2.3fold activation, binding of 3 Mg(II) per subunit
Mg2+
-
2 Mg2+ binding sites per subunit
Mg2+
-
implicated in quarternary structure
Mg2+
-
20-30% stimulation at pH 8.5, no requirement for a metal ion
Mg2+
-
stimulates but is not required for activity. Eight Mg2+ ions can be seen in the crystal structure, one per monomer, all bound at the allosteric magnesium-binding site. No metal ion can be seen in the active site
Mg2+
-
binds only 4 Mg2+ per octamer, these 4 Mg2+ allosterically stimulate a metal ion independent catalytic actiovity, in a fashion dependent upon both pH and K+, the allosteric Mg2+ is located in metal binding site C, which is outside the active site. NO evidence is found for metal binding to the potential high-affinity active site metal binding site A and/or B, no direct involvement of Mg2+ in substrate binding and product formation
Mg2+
-
can completrly restore activity after inhibition by EDTA
Mg2+
-
can completrly restore activity after inhibition by EDTA, stabilizes the oligomeric state but is not essential for octamer formation
Mg2+
enzyme contains Mg2+ in the active site
Mg2+
-
enzyme responds to Mg2+ but not to Zn2+, enzyme shows two Mg2+ affinities
Mn2+
-
activates
Mn2+
-
can reactivate the demetallated protein
Mn2+
-
can reactivate the demetallated protein
Ni(2+)
-
0.15 mM, activates
Ni(2+)
-
about 70% reactivation of the demetalled protein
Ni2+
-
partially restores activity after inhibition with EDTA
Zinc
-
contains 1 gatom of zinc per mol of subunit, zinc has a structural rather than a direct catalytic role
Zinc
-
lacks a catalytic ZnA, enzyme can bind Zn(II), presumably as ZnA, at a stoichiometry of 4/octamer with a Kd of 0.2 mM, this high concentration is outside the physiologically significant range
Zinc
-
Zn(II) metalloenzyme, Zn(II) is required for catalytic activity
Zinc
-
4 Zn at metal binding site A , 4 Zn at metal binding site B and 8 Mg at metal binding site C are required for full activity per homooctamer
Zinc
-
4 Zn at metal binding site A and 4 Zn at metal binding site B are required for full activity per homooctamer
Zinc
-
binds 8 mol of zinc per mol of octamer, zinc may interact with one or more of the highly reactive enzyme thiol groups
Zinc
-
4 Zn at metal binding site A and 8 Mg at metal binding site C are required for full activity per homooctamer
Zinc
8 Zn at metal binding site A and 8 Zn at metal binding site B are required for full activity per homooctamer
Zn2+
-
required
Zn2+
-
Zn2+ forms a bond with a sulfhydryl group in the enzyme, the octameric enzyme contains 4 gatom of Zn2+ per mol of enzyme, Zn2+ does not participate in substrate binding nor in the maintenance of the quarternary structure of the enzyme
Zn2+
-
2 mol of Zn2+ bound per mol of subunit
Zn2+
enzyme uses a catalytic Zn2+
Zn2+
-
0.5 mM, 10% increase in activity
Zn2+
-
optimal activation by 0.1-0.3 mM ZnCl2
Zn2+
-
activates at 0.1-0.02 mM, inhibits at 1.0 mM
Zn2+
the cysteines of the metal switch sequence of the wild-type enzyme bind a catalytic zinc. Chimeric proteins are constructed that contain the aspartate-rich sequences of the pea enzyme or the enzyme from Pseudomonas aeruginosa in place of the naturally occuring cysteine-rich sequence of the human enzyme. The chimeric enzymes are substantially activated by both magnesium and potassium, but not by zinc.
Zn2+
-
optimal stimulation at 0.1 mM
Zn2+
-
required for activity
Zn2+
-
inhibits enzymatic activity
Zn2+
-
partially restores activity after inhibition with EDTA
Zn2+
requires exogenous thiols and zinc ions for optimal activity. 0.7 zinc ions per mol of subunit
Zn2+
-
delta-ALA-D is a metalloenzyme requiring zinc for activation
Zn2+
-
activity is progressively increased with increasing Zn2+ concentrations up to 0.1 mM, inhibition at high concentrations
Zn2+
-
required for catalysis, bound at the active site
Zn2+
-
restores enzyme after inactivation by 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedisulfonate
additional information
-
zinc is apparently not a cofactor
additional information
-
no stimulation by Mg2+
additional information
-
does not require metallic cations for activation
additional information
does not utilize metal ions such as Zn2+ or Mg2+
additional information
-
does not utilize metal ions such as Zn2+ or Mg2+
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(4E)-6-oxodec-4-enedioic acid
-
-
1,1',1''-[(3-ethoxyprop-1-ene-1,1,2-triyl)triselanyl]tribenzene ethyl 2,3,3-tris(phenylselanyl)prop-2-en-1-yl ether
-
0.6 mM, 65% inhibition
1,1',1''-[(3-ethoxyprop-1-ene-1,1,2-triyl)triselanyl]tris(2,4,6-trimethylbenzene) ethyl 2,3,3-tris[(2,4,6-trimethylphenyl)selanyl]prop-2-en-1-yl ether
-
0.6 mM, 44% inhibition
1,1',1''-[(3-ethoxyprop-1-ene-1,1,2-triyl)triselanyl]tris(4-chlorobenzene) ethyl 2,3,3-tris[(4-chlorophenyl)selanyl]prop-2-en-1-yl ether
-
modest inhibition
1-amino-4-hydroxy-2-butanone
-
-
1-amino-4-methoxy-2-butanone
-
-
1-amino-5-hydroxy-2-pentanone
-
-
2,2-difluorosuccinic acid
-
competitive
2,3-dimercaptopropane-1-sulfonic acid
2,3-Dimercaptopropanol
-
cysteine and ZnCl2 protects. Dithiothreitol protects inhibition by 1 mM 2,3-dimercaptopropanol in a concentration dependent manner
2-bromo-3-(imidazol-5-yl)propionic acid
-
-
3-acetyl-4-oxoheptane-1,7-dioic acid
-
formation of a Schiff base complex between the inhibitors and the active site Lys
4,7-dioxosebacic acid
-
hanging-drop method, irreversible inhibitor binds by forming Schiff-base linkages with lysines 200 and 253 at the active site. 4,7-dioxosebacic acid is a better inhibitor of the zinc-dependent 5-aminolaevulinic acid dehydratases than of the zinc-independent 5-aminolaevulinic acid dehydratases
4-amino-3-oxobutanoate
-
-
4-oxosebaic acid
active site-directed irreversible inhibitor, less potent than 4,7-dioxosebaic acid
5,5'-dithio(bis-2-nitrobenzoic acid)
-
-
5,5'-dithiobis(2-nitrobenzoic acid)
-
-
5,5'-iminobis(4-oxopentanoic acid)
5,5'-oxybis(4-oxopentanoic acid)
5,5'-sulfinylbis(4-oxopentanoic acid)
5,5'-sulfonylbis(4-oxopentanoic acid)
5,5'-thiobis(4-oxopentanoic acid)
5-amino-4-oxopentanenitrile
-
-
5-bromo-levulinic acid
-
-
5-bromolevulinic acid
-
-
5-fluorolevulinic acid
both inhibitor molecules are covalently bound to two conserved, active-site lysine residues, Lys205 and lys260, through Schiff bases
5-hydroxy-4-oxo-L-norvaline
-
competitive
5-hydroxy-4-oxopentanoic acid
-
-
5-hydroxylaevulinic acid
the competitive inhibitor is bound by a Schiff-base link to one of the invariant active-site lysine residues (Lys263). The inhibitor appears to bind in two well defined conformations
5-hydroxylevulinate
-
competitive
5-hydroxylevulinic acid
-
5-nitrilo-4-oxopentanoic acid
-
-
6-amino-5-oxohexanoic acid
-
-
7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
using in silico screening two hexamer-stabilizing inhibitors of PBGS are identified: N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide and 7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
8-Hydroxyquinoline-5-sulfonic acid
-
-
Al2(SO4)3
-
ALA-D inhibition may be due to the fact that aluminum present in the growth medium can compete with Mg2+ or reduce the expression of ALA-D
Al3+
-
IC50: 0.319 mM, GSH has no protective effect
alaremycin
porphobilinogen synthase is cocrystallized with the alaremycin. At 1.75 A resolution, the crystal structure reveals that the antibiotic efficiently blocks the active site of porphobilinogen synthase. The antibiotic binds as a reduced derivative of 5-acetamido-4-oxo-5-hexenoic acid. The corresponding methyl group is not coordinated by any amino acid residues of the active site, excluding its functional relevance for alaremycin inhibition. Alaremycin is covalently bound by the catalytically important active-site lysine residue 260 and is tightly coordinated by several active-site amino acids
AlCl3
-
0.001-0.01 mM AlCl3
alloxan
-
i.e. 2,4,5,6-tetraoxypyrimidine 5,6-dioxyuracil , 0.00125-0.02 mM alloxan causes a concentration-dependent uncompetitive inhibition. Dithiothreitol (0.7and 1 mM) completely prevents the inhibition induced by 0.01 and 0.02 mM alloxan. Similar protection is obtained in the presence of 2 mMglutathione
alpha-lipoic acid
-
significant inhibition
arsenic acid
-
inhibition of 5-aminolevulinic acid dehydratase activity by arsenic in excised etiolated maize leaf segments during greening. KNO3, chloramphenical, cycloheximide, DTNB and levulinic aciddecrease inhibition. GSH increase inhibition
ascorbic acid
-
0.4 mM, 23% inhibition
bathocuproine disulfonic acid
bis(4-chlorophenyl)diselenide
-
-
bis(4-methoxyphenyl)diselenide
-
-
bis[3-(trifluoromethyl)phenyl]diselenide
-
-
Butanedione
-
protection by 5-aminolevulinate
Carbonate
-
using a carbonate buffer rather than phosphate causes nearly a 90% drop in activity in the developed assay method
Coproporphyrinogen III
-
-
Cuprizone
-
bis-cyclohexanoneoxaldihydrazone
D-fructose
-
formation of a Schiff base with the critical lysine residue of the enzyme is involved in inhibition of the enzyme by hexoses and pentoses
D-ribose
-
formation of a Schiff base with the critical lysine residue of the enzyme is involved in inhibition of the enzyme by hexoses and pentoses
diammine(dichloro)platinum
-
mechanism of inhibition is a direct interaction of the inhibitor with sulfhydryl groups, whereas zinc site appears to be involved with the higher doses only
dicholesteroyl diselenide
-
significant at 0.1 mM
diethyldithiocarbamate
-
-
diphenyl ditelluride
-
dithiothreitol protects
DTNB
-
reversible loss of activity
ebselen
-
dithiothreitol protects
Ga3+
-
inhibits by competing with Zn2+, IC50: 0.442 mM, GSH has no protective effect, Zn2+ completely recovers inhibition
HgCl2
-
pretreatment with a nontoxic dose of Na2SeO3 partially or totally prevents in vivo mercury effects in kidney, including prevention of inhibition of delta-aminolevulinate dehydratase
In3+
-
inhibits by competing with Zn2+, IC50: 0.298 mM, GSH reduces inhibition, DL-dithiothreitol has modest effect on inhibition, Zn2+ completely recovers inhibition
meso-2,3-dimercaptosuccinic acid
methyl methanethiosulfonate
-
-
N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide
using in silico screening two hexamer-stabilizing inhibitors of PBGS are identified: N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide and 7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
Na2SeO3
-
inhibits renal and hepatic enzyme
Neocuproine
-
2,9-dimethyl-1,10-phenanthroline
Ni2+
-
0.5 mM, 8% inhibition
p-hydroxymercuribenzoate
-
-
phenyl selenoxideacetylene
phosphate
-
competitive against Mg2+
protoporphyrinogen IX
-
feedback inhibition by downstream intermediate
pyridoxamine phosphate
-
-
rac-2-hydroxy-4-oxopentanoic acid
-
-
rac-3-hydroxy-4-oxopentanoic acid
-
-
succinic acid
-
noncompetitive
succinic acid monomethyl ester
-
competitive
Tl3+
-
inhibits by direct oxidation of essential sulfhydryl groups, IC50: 0.0085 mM, DL-dithiothreitol restores completely enzyme activity inhibited by Tl3+, Zn2+ is unable to change inhibition
1,10-phenanthroline
-
-
2,3-dimercaptopropane-1-sulfonic acid
-
1 mM, 0.5 mM ZnCl2 protects but does not reverse inhibition. Dithiothreitol protects inhibition by 1 mM 2,3-dimercaptopropane-1-sulfonic acid in a concentration dependent manner
2,3-dimercaptopropane-1-sulfonic acid
-
in presence of Hg2+ or Cd2+ the inhibitory potency increases, no change in inhibitory potency by inclusion of Pb2+, Zn2+ does not modify the inhibitory effect
2,3-dimercaptopropane-1-sulfonic acid
-
0.1 mM, 20% inhibition, more pronounced inhibition in combination with Cd2+
5,5'-iminobis(4-oxopentanoic acid)
-
5,5'-iminobis(4-oxopentanoic acid)
-
-
5,5'-oxybis(4-oxopentanoic acid)
-
5,5'-oxybis(4-oxopentanoic acid)
-
-
5,5'-sulfinylbis(4-oxopentanoic acid)
-
5,5'-sulfinylbis(4-oxopentanoic acid)
-
-
5,5'-sulfonylbis(4-oxopentanoic acid)
-
5,5'-sulfonylbis(4-oxopentanoic acid)
-
-
5,5'-thiobis(4-oxopentanoic acid)
-
5,5'-thiobis(4-oxopentanoic acid)
-
-
5-chlorolevulinic acid
-
-
5-chlorolevulinic acid
-
inactivation results fromthe initial formation of a Schiff base with lysine-247, followed by alkylation of lysine-195 by the resulting reactive chloroimide
bathocuproine disulfonic acid
-
-
bathocuproine disulfonic acid
-
i.e. 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedisulfonate
Cd2+
-
inhibition at low concentration of substrate and stimulation at high levels of substrate
Cd2+
-
0.5 mM, 9% inhibition
Cd2+
-
0.1 mM Cd2+ totally inhibits enzyme activity. Dithiothreitol (0.003 mM) is able to restore the inhibition of enzyme activity caused by Cd2+ (0.02 mM)
Cd2+
-
inhibits delta-ALA-D activity. Chelating and antioxidant agents potentiated the inhibition
Cd2+
-
enzyme inhibition in excised etiolated leaf segments during greening. Cd2+ inhibits ALAD activity by affecting the ALA binding to the enzyme and/or disrupting thiol interaction. Inhibition of ALAD activity by Cd2+ is decreased in the presence of nitrogenous compounds, glutamine and NH4NO3, overview. Supply of some essential metal ions, such as Mg2+, Zn2+, and Mn2+, also reduces the inhibition of enzyme activity by Cd2+
Co2+
-
0.5 mM, 15% inhibition
Cu2+
-
-
D-glucose
-
competitive inhibitor for ALA dehydratase
D-glucose
-
formation of a Schiff base with the critical lysine residue of the enzyme is involved in inhibition of the enzyme by hexoses and pentoses
D-glucose
-
incubations of erythrocytes for 24 h with glucose results in an increase of delta-ALA-D activity. Incubations of erythrocytes with 100 to 200 mM glucose for 48 h inhibit delta-ALA-D activity
dibutyl diselenide
-
IC50: 0.01 mM
dibutyl diselenide
-
IC50: 0.693 mM, enzyme from liver; IC50: 0.985 mM, enzyme from gill
diphenyl diselenide
-
dithiothreitol protects
diphenyl diselenide
-
IC50: 0.007 mM
diphenyl diselenide
-
0.0005 mM, 17% inhibition
diphenyl diselenide
-
significantl inhibition
diphenyl diselenide
-
significant at 0.001 mM
diphenyl diselenide
-
IC50: 0.076 mM, enzyme from liver; IC50: 0.274 mM, enzyme from gill
EDTA
-
-
EDTA
-
0.3 mM, 51% inhibition
EDTA
-
5 mM, 90% inhibition
EDTA
-
activity can be completely restored by addition of Mg2+ or Mn2+. Co2+, Zn2+, and Ni2+ partially restore EDTA-inhibited activity
Hg2+
-
inhibitory effect is increased by meso-2,3-dimercaptosuccinic acid, inhibition is prevented by dithiothreitol
Hg2+
-
inhibits enzyme in vivo at 6 h and 12 h after treatment. Se4+ abolishes the inhibitory effect of Hg2+
Hg2+
-
the inhibition caused by 0.37 mM Hg2+ is alleviated by addition of 10 mM KNO3. 10 mM NH4Cl and 5 mM sucrose increase the inhibitory effect of Hg2+ on enzyme activity, while 10 mM levulinic acid and 0.0001 mM 5,5'-dithio(bis-2-nitrobenzoic acid) glutamine and glutathione decrease it
iodoacetamide
-
irreversible
iodoacetamide
-
1 mM, 97% inhibition
iodoacetamide
-
insensitive
iodoacetate
-
irreversible
levulinic acid
-
levulinic acid
-
competitive
levulinic acid
-
a weak competitive inhibitor
levulinic acid
-
competitive inhibitor, 8% residual activity at 20 mM
meso-2,3-dimercaptosuccinic acid
-
4 mM, 1 mM ZnCl2 protects but does not reverse inhibition. Dithiothreitol protects inhibition by 1 mM meso-2,3-dimercaptosuccinic acid in a concentration dependent manner
meso-2,3-dimercaptosuccinic acid
-
in presence of Hg2+ or Cd2+ the inhibitory potency increases, Zn2+ does not modify the inhibitory effect
meso-2,3-dimercaptosuccinic acid
-
0.1 mM, 18% inhibition
Mg2+
-
0.5 mM, 7% inhibition
Mn2+
-
0.5 mM, 21% inhibition
NaCN
-
competitive
NaCN
-
in presence of the substrate
NEM
-
1 mM, 85% inhibition
Pb2+
-
does not produce a change in the quarternary structure detectable by small angle X-ray scattering
Pb2+
-
0.5 mM, 44% inhibition
Pb2+
-
5-aminolevulinate protects
PCMB
-
1 mM, 97% inhibition
phenyl selenoacetylene
-
IC50: above 0.4 mM
phenyl selenoacetylene
-
IC50: 0.25 mM
phenyl selenoacetylene
-
inhibition involves conversion of phenyl selenoacetylene to diphenyl diselenide, that induces oxidation of essential -SH groups of the enzyme. Inhibition is partially prevented by incubation under argon atmosphere and is completely prevented by dithiothreitol
phenyl selenoxideacetylene
-
IC50: 0.1 mM, inhibition is antagonized by dithiothreitol
phenyl selenoxideacetylene
-
IC50: 0.045 mM, inhibition is antagonized by dithiothreitol
pyridoxal 5'-phosphate
-
30% inhibition at 1 mM, negligible inhibition at 0.05 mM
pyridoxal 5'-phosphate
-
competitive
sodium selenide
-
IC50: 0.005 mM
sodium selenide
-
IC50: 0.386 mM, enzyme from gill; IC50: 0.902 mM, enzyme from liver
succinylacetone
-
50% inhibition by 125 nM
succinylacetone
-
50% inhibition by 250 nM
Zn2+
-
-
Zn2+
-
the inhibitory zinc is located at a subunit interface using Cys219 and His10 as ligands
Zn2+
-
activates at 0.1-0.02 mM, inhibits at 1.0 mM
Zn2+
-
exocenous addition of zinc results in a decrease by up to 35% in enzyme activity
Zn2+
-
pH 7.5, 50% inhibition at 0.12 mM
Zn2+
-
at pH 8.5, 50% inhibition by 0.075 mM. At pH 7.5, 50% inhibition by less than 0.02 mM
Zn2+
-
activity is progressively increased with increasing Zn2+ concentrations up to 0.1 mM, inhibition at high concentrations
additional information
-
the enzyme from human erythrocytes is a potential target for organochalcogens
-
additional information
-
not inhibited by Seleno-furanoside
-
additional information
-
no inhibition by EDTA even at 25 mM
-
additional information
-
no inhibition by dicholesteroyl diselenide
-
additional information
-
in vivo iron reduction in rat blood has a negative correlation with the activity of delta-ALA-D, overview
-
additional information
-
insensitive to inhibition by hemin and protoporphyrin
-
additional information
no inhibition by 10 mM EDTA or 1,20-phenanthroline
-
additional information
-
no inhibition by 10 mM EDTA or 1,20-phenanthroline
-
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30
1-amino-4-methoxy-2-butanone
Rattus sp.
-
-
32.5
1-amino-5-hydroxy-2-pentanone
Rattus sp.
-
-
0.31
5,5'-iminobis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
0.96
5,5'-oxybis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
38
5,5'-sulfinylbis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
9.9
5,5'-sulfonylbis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
0.34
5,5'-thiobis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
0.01
7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
Homo sapiens
-
0.319
Al3+
Bos taurus
-
IC50: 0.319 mM, GSH has no protective effect
1.33
alaremycin
Pseudomonas aeruginosa
-
0.004
alloxan
Mus musculus
-
pH 6.4 and 37°C
0.01 - 0.985
dibutyl diselenide
0.00195 - 0.274
diphenyl diselenide
0.442
Ga3+
Bos taurus
-
inhibits by competing with Zn2+, IC50: 0.442 mM, GSH has no protective effect, Zn2+ completely recovers inhibition
0.298
In3+
Bos taurus
-
inhibits by competing with Zn2+, IC50: 0.298 mM, GSH reduces inhibition, DL-dithiothreitol has modest effect on inhibition, Zn2+ completely recovers inhibition
0.058
N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide
Homo sapiens
-
0.25 - 0.4
phenyl selenoacetylene
0.045 - 0.1
phenyl selenoxideacetylene
0.005 - 0.902
sodium selenide
0.001
succinylacetone
Toxoplasma gondii
-
-
0.0085
Tl3+
Bos taurus
-
inhibits by direct oxidation of essential sulfhydryl groups, IC50: 0.0085 mM, DL-dithiothreitol restores completely enzyme activity inhibited by Tl3+, Zn2+ is unable to change inhibition
0.01917
Cd2+
Mus musculus
-
at pH 6.8 and 37°C
0.0345
Cd2+
Rattus norvegicus
-
pH 6.8, 37°C
0.01
dibutyl diselenide
Rattus norvegicus
-
IC50: 0.01 mM
0.693
dibutyl diselenide
Rhamdia quelen
-
IC50: 0.693 mM, enzyme from liver
0.985
dibutyl diselenide
Rhamdia quelen
-
IC50: 0.985 mM, enzyme from gill
0.00195
diphenyl diselenide
Mus musculus
-
37°C, pH 6.5
0.007
diphenyl diselenide
Rattus norvegicus
-
IC50: 0.007 mM
0.076
diphenyl diselenide
Rhamdia quelen
-
IC50: 0.076 mM, enzyme from liver
0.274
diphenyl diselenide
Rhamdia quelen
-
IC50: 0.274 mM, enzyme from gill
0.0056
Pb2+
Mus musculus
-
37°C, pH 8.5
0.0062
Pb2+
Mus musculus
-
37°C, pH 6.5
0.25
phenyl selenoacetylene
Rattus norvegicus
-
IC50: 0.25 mM
0.4
phenyl selenoacetylene
Cucumis sativus
-
IC50: above 0.4 mM
0.045
phenyl selenoxideacetylene
Rattus norvegicus
-
IC50: 0.045 mM, inhibition is antagonized by dithiothreitol
0.1
phenyl selenoxideacetylene
Cucumis sativus
-
IC50: 0.1 mM, inhibition is antagonized by dithiothreitol
0.005
sodium selenide
Rattus norvegicus
-
IC50: 0.005 mM
0.386
sodium selenide
Rhamdia quelen
-
IC50: 0.386 mM, enzyme from gill
0.902
sodium selenide
Rhamdia quelen
-
IC50: 0.902 mM, enzyme from liver
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183500
mutant enzyme R240A, pH 9, analytical ultracentrifugation
188500
mutant enzyme R240A, pH 7, analytical ultracentrifugation
197000
variant F12L, equilibrium sedimentation
197900
mutant enzyme F12L, pH 7, analytical ultracentrifugation
212400
mutant enzyme R240A, pH 7, dynamic light scattering
214400
mutant enzyme F12L, pH 7, dynamic light scattering
220000
gel filtration, analytical ultracentrifugation
275000
-
glycerol density gradient centrifugation
289000
-
equilibrium sedimentation
30000
-
8 * 30000, SDS-PAGE
31000
-
8 * 31000, SDS-PAGE
317600
wild-type enzyme, pH 7, dynamic light scattering
32000
-
subunit of L273R, analyzed by SDS-PAGE
320000
-
gel filtration, recombinant TgPBGS is purified as a stable octamer
324000
-
density gradient centrifugation
34800
-
analyzed by SDS-PAGE
34900
-
8 * 34900, equilibrium sedimentation in presence of 6 M guanidine-HCl
35856
6 * 35856, calculation from nucleotide sequence
36690
-
theoretical monomer molecular mass
37832
-
6 * 37832, electrospray ionization mass spectrometry
42000
-
6 * 42000, SDS-PAGE
43000
-
8 * 43000, SDS-PAGE
45000
-
x * 45000, SDS-PAGE
46000
-
8 * 46000, mature recombinant enzyme, SDS-PAGE
50000
-
6 * 50000, SDS-PAGE
69600
mutant enzyme W19A, pH 7, analytical ultracentrifugation
78600
mutant enzyme W19A, pH 7, dynamic light scattering
244000
wild-type enzyme, equilibrium sedimentation
244000
wild-type enzyme, pH 7, analytical ultracentrifugation
260000
-
sucrose density gradient centrifugation
260000
-
low-speed equilibrium sedimentation
280000
-
-
282000
-
gel filtration
282000
-
measurement of sedimentation velocity
35000
-
8 * 35000, SDS-PAGE
35000
-
8 * 35000, SDS-PAGE
36000
-
subunit, analyzed by SDS-PAGE
36000
-
8 * 36000, SDS-PAGE
36000
-
8 * 36000, SDS-PAGE
37000
-
x * 37000, maximally active octamer can dissociate into less active smaller subunits, minimal functional unit is a tetramer, SDS-PAGE
37000
-
8 * 37000, SDS-PAGE
38000
-
x * 38000, SDS-PAGE
38000
-
8 * 38000, mature recombinant enzyme, SDS-PAGE
40000
-
6 * 40000, SDS-PAGE
40000
-
recombinant TgPBGS also shows low levels of dimers, 2 * 40000 Da, SDS-PAGE
40000
-
recombinant TgPBGS is purified as a stable octamer, 8 * 40000 Da, SDS-PAGE
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
the enzyme is incorporated into mitochondria at a size of 170000 Da and then is gradually converted to a size of 110000 Da, within the mitochondria, hemin stimulates the aggregation of the enzyme in cytosol to a size of 700000 Da
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hexamer or octamer
-
by analytical ultracentrifugation
?
-
x * 38000, SDS-PAGE
?
-
x * 37000, maximally active octamer can dissociate into less active smaller subunits, minimal functional unit is a tetramer, SDS-PAGE
?
x * 37676, mass spectroscopy
?
-
x * 37676, mass spectroscopy
-
dimer
-
dimer
pro-hexamer dimer and pro-octamer dimer, analyzed by gel filtration
dimer
-
recombinant TgPBGS also shows low levels of dimers, 2 * 40000 Da, SDS-PAGE
hexamer
-
6 * 40000, SDS-PAGE
hexamer
wild type, pH 8.8, catalytic turnover favors octamer, analyzed by gel filtration and anion exchange chromatography
hexamer
hexameric structure of the enzyme only shows low activity. Using in silico screening two hexamer-stabilizing inhibitors of PBGS are identified: N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide and 7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
hexamer
6 * 35856, calculation from nucleotide sequence
hexamer
-
6 * 50000, SDS-PAGE
hexamer
-
6 * 42000, SDS-PAGE
octamer
-
8 * 36000, SDS-PAGE
octamer
-
8 * 34900, equilibrium sedimentation in presence of 6 M guanidine-HCl
octamer
-
8 * 35000, SDS-PAGE
octamer
-
8 * 36000, SDS-PAGE
octamer
-
8 * 35000, SDS-PAGE
octamer
-
8 * 31000, SDS-PAGE
octamer
the enzyme is an obligate oligomer that can exist in functionally distinct quaternary states of different stoichiometries, which are called morpheeins, human PBGS assembles into long-lived morpheeins and is capable of forming either a high activity octamer or a low activity hexamer
octamer
wild type, pH 6.9 and pH 8.8, analyzed by gel filtration and anion exchange chromatography
octamer
high activity octamer is the dominant assembly
octamer
-
8 * 30000, SDS-PAGE
octamer
-
8 * 38000, mature recombinant enzyme, SDS-PAGE
octamer
-
8 * 43000, SDS-PAGE
octamer
-
8 * 46000, mature recombinant enzyme, SDS-PAGE
octamer
-
6 * 37832, electrospray ionization mass spectrometry
octamer
-
8 * 37000, SDS-PAGE
octamer
-
recombinant TgPBGS is purified as a stable octamer, 8 * 40000 Da, SDS-PAGE
additional information
-
-
additional information
-
dissociation and reassociation of the subunits of immobilized PGB synthase
additional information
wild-type enzyme and variant F12L exist in different oligomeric states. The wild-type enzyme exists as an octamer and the F12L variant exists as a hexamer. It appears that any equilibrium between octamer and hexamer most probably proceeds through the interconversion of hugging dimer and the detached dimer
additional information
-
wild-type enzyme and variant F12L exist in different oligomeric states. The wild-type enzyme exists as an octamer and the F12L variant exists as a hexamer. It appears that any equilibrium between octamer and hexamer most probably proceeds through the interconversion of hugging dimer and the detached dimer
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H10F
-
mutant enzyme is active but is not inhibited by zinc. H10F binds a catalytic zinc at 0.5/subunit and binds a second nonessential and noninhibitory zinc at 0.5/subunit
K195A
-
mutant enzyme with only 0.1% of the wild-type activity
K195C
-
mutant enzyme with only 0.1% of the wild-type activity, 2-bromethylamine results in recovery of 10% of the wild-type activity
K247A
-
inactive mutant enzyme
K247C
-
inactive mutant enzyme, 2-bromethylamine results in recovery of 6% of the wild-type activity
A274K
naturally occurring ALAD porphyria-associated human PBGS mutants are shown to have an increased susceptibility to inhibition by both N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide and 7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
C132R
-
enzyme activity undetectable
G133R
-
11% of wild-type activity
K59N
-
112% of wild-type activity
K59N/G133R
-
22% of wild-type activity
L273R
-
enzyme activity undetectable
R221K
mutation in wild-type or chimeric enzymes reduces activity
R240A
mutant enzyme assembles into a metastable hexamer, which can undergo a reversible conversion to the octamer in the presence of substrate
R240AS
metastable nature of the R240A hexamer
V153M
-
about 67% of wild-type activity
W19A
assembles into a mixture of stable dimers
C326A
-
no effect on enzymatic activity
DELTA646-658
-
a mutant enzyme lacking the C-terminal 13 amino acids distinguishing parasite PBGS from plant and animal enzymes is purified as a dimer, suggesting that the C-terminus is required for octamer stabilisation
E89K
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75% of wild-type activity
E89K
naturally occurring ALAD porphyria-associated human PBGS mutants are shown to have an increased susceptibility to inhibition by both N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide and 7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
F12L
the catalytic activity is very low under conditions at which the wild-type human enzyme is most active
F12L
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enzyme activity undetectable
F12L
naturally occurring variant
F12L
low activity mutant F12L shows a hexameric structure, mutant F12L is used for in silico screening of 111000 structures for hexamer-stabilizing inhibitors
additional information
chimeric proteins that contain the aspartate-rich sequences of the pea enzyme or the enzyme from Pseudomonas aeruginosa in place of the naturally occuring cysteine-rich sequence of the human enzyme. The chimeric enzymes are substantially activated by both magnesium and potassium, but not by zinc. The specific activities of the chimeras are significantly lower than the specific activity of the wild-type enzyme
additional information
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chimeric proteins that contain the aspartate-rich sequences of the pea enzyme or the enzyme from Pseudomonas aeruginosa in place of the naturally occuring cysteine-rich sequence of the human enzyme. The chimeric enzymes are substantially activated by both magnesium and potassium, but not by zinc. The specific activities of the chimeras are significantly lower than the specific activity of the wild-type enzyme
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synthesis
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in addition to hemA and hemL, hemB, hemD, hemF, hemG and hemH are also major regulatory targets of the heme biosynthesis pathway. Up-regulation of hemD and hemF benefits ALA accumulation whereas overexpression of hemB, hemG and hemH diminishes ALA accumulation. By combinatorial overexpression of hemA, hemL,hemD and hemF with different copy-number plasmids, the titer of ALA can be improved to 3.25 g/l
analysis
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measurement of ethanol consumption in alcoholics
analysis
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indirect measurement of blood lead in human subjects
analysis
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the enzyme can be used as a biomarker for Pb2+ contamination
diagnostics
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the DELTA-aminolevulinic acid dehydratase test of blood is valid and representative for low-level as well as long-term exposure to lead. The test might be applicable to diagnostic purposes and screening of the population having been exposed to low-level lead over a long-term period
diagnostics
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the enzyme activity is a diagnostic marker for the clinical diagnosis of delta-aminolevulinic acid dehydratase-deficient porphyria, a rare enzymatic deficiency of the heme biosynthetic pathway
environmental protection
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the enzyme can be used as a biomarker for Pb2+ contamination
environmental protection
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in free-living bird species, a decrease is observed in ALAD activity in Griffon vultures and Eagle owls exposed to Pb. Negative relationships are found between ALAD ratio or ALAD activity and logarithmic blood Pb levels in Griffon vultures and Eagle owls, and these relationships are stronger in areas with the highest Pb exposure. ALAD activity in Slender-billed gull and Audouin's gull species may be considerably normal, since very low blood Pb concentrations and no correlations are found
environmental protection
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in free-living bird species, a decrease is observed in ALAD activity in Griffon vultures and Eagle owls exposed to Pb. Negative relationships are found between ALAD ratio or ALAD activity and logarithmic blood Pb levels in Griffon vultures and Eagle owls, and these relationships are stronger in areas with the highest Pb exposure. ALAD activity in Slender-billed gull and Audouin's gull species may be considerably normal, since very low blood Pb concentrations and no correlations are found
environmental protection
-
in free-living bird species, a decrease is observed in ALAD activity in Griffon vultures and Eagle owls exposed to Pb. Negative relationships are found between ALAD ratio or ALAD activity and logarithmic blood Pb levels in Griffon vultures and Eagle owls, and these relationships are stronger in areas with the highest Pb exposure. ALAD activity in Slender-billed gull and Audouin's gull species may be considerably normal, since very low blood Pb concentrations and no correlations are found
environmental protection
-
in free-living bird species, a decrease is observed in ALAD activity in Griffon vultures and Eagle owls exposed to Pb. Negative relationships are found between ALAD ratio or ALAD activity and logarithmic blood Pb levels in Griffon vultures and Eagle owls, and these relationships are stronger in areas with the highest Pb exposure. ALAD activity in Slender-billed gull and Audouin's gull species may be considerably normal, since very low blood Pb concentrations and no correlations are found
medicine
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delta-ALA-D activity is a reliable marker for oxidative stress in bone marrow transplantation patients
medicine
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in blood samples from patients previously treated for lung cancer with chemotherapy, ALAD activity shows a 37% decrease compared with control. Reactive species and thiobarbituric acid reactive substances are 8% and 99% higher in the patient group, respectively. The activity of superoxide dismutase and catalase as well as the vitamin C content are 41%, 35% and 127% lower in patients when compared with controls, respectively. Total thiols and vitamin E levels are 27% and 44% higher in lung cancer patients, respectively