Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 1.1.1.205 extracted from

  • Gan, L.; Petsko, G.A.; Hedstrom, L.
    Crystal structure of a ternary complex of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase: NAD+ orients the active site loop for catalysis (2002), Biochemistry, 41, 13309-13317.
    View publication on PubMed
Search for more literature for 1.1.1.205

Application

Application Comment Organism
drug development the enzyme is a potential therapeutic target, and the NAD+ site may be an exploitable target for the design of antimicrobial drugs Tritrichomonas suis

Cloned(Commentary)

Cloned (Comment) Organism
expression of the full-length enzyme and the alphabeta core domain of the enzyme in Escherichia coli Tritrichomonas suis

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant full-length enzyme and alphabeta core domain in complex with inosine 5'-phosphate and beta-methylene-thiazole-4-carboxamide adenine dinucleotide, X-ray diffraction structure determination and analysis at 2.2 A resolution, molecular replacement Tritrichomonas suis

Inhibitors

Inhibitors Comment Organism Structure
beta-methylene-thiazole-4-carboxamide adenine dinucleotide i.e. beta-Me-TAD, enzyme binding structure analysis, the enzyme active site loop is ordered in this complex, and the catalytic Cys319 is 3.6 A from IMP, in the same plane as the hypoxanthine ring, the active site loop forms hydrogen bonds to the carboxamide of beta-Me-TAD, overview Tritrichomonas suis
additional information structural basis of the drug selectivity, overview Tritrichomonas suis
Mycophenolic acid i.e. MPA, slight inhibition, microbial IMPDHs differ from mammalian enzymes in their lower affinity for inhibitors such as mycophenolic acid and thiazole-4-carboxamide adenine dinucleotide, part of this resistance is determined by the coupling between nicotinamide and adenosine subsites in the NAD+ binding site that is postulated to involve an active site flap Tritrichomonas suis
NAD+
-
 Tritrichomonas suis
thiazole-4-carboxamide adenine dinucleotide i.e. TAD, slight inhibition, microbial IMPDHs differ from mammalian enzymes in their lower affinity for inhibitors such as mycophenolic acid and thiazole-4-carboxamide adenine dinucleotide, part of this resistance is determined by the coupling between nicotinamide and adenosine subsites in the NAD+ binding site that is postulated to involve an active site flap Tritrichomonas suis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0017
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis
0.0024
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant alphabeta core domain, in absence of 100 mM KCl Tritrichomonas suis
0.0026
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant full-length enzyme, in absence of 100 mM KCl Tritrichomonas suis
0.003
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
0.11
-
 NAD+ pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
0.15
-
 NAD+ pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis
1.1
-
 NAD+ pH 8.0, 25°C, recombinant full-length enzyme, in absence of 100 mM KCl Tritrichomonas suis
1.2
-
 NAD+ pH 8.0, 25°C, recombinant alphabeta core domain, in absence of 100 mM KCl Tritrichomonas suis

Metals/Ions

Metals/Ions Comment Organism Structure
K+ strong activation, the K+ site is observed at the subunit interface, the activation is linked to NAD+ Tritrichomonas suis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
inosine 5'-phosphate + NAD+ + H2O Tritrichomonas suis rate-limiting step of the de novo guanine nucleotide biosynthesis xanthosine 5'-phosphate + NADH
-
 ?

Organism

Organism UniProt Comment Textmining
Tritrichomonas suis
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant full-length enzyme and alphabeta core domain of the enzyme from Escherichia coli Tritrichomonas suis

Reaction

Reaction Comment Organism Reaction ID
IMP + NAD+ + H2O = XMP + NADH + H+ substrate binding and catalytic reaction mechanism, Cys319 is the catalytic residue, NAD+ promotes the nucleophilic attack of Cys319 on IMP Tritrichomonas suis
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
inosine 5'-phosphate + NAD+ + H2O
-
 Tritrichomonas suis xanthosine 5'-phosphate + NADH
-
 ?
inosine 5'-phosphate + NAD+ + H2O rate-limiting step of the de novo guanine nucleotide biosynthesis Tritrichomonas suis xanthosine 5'-phosphate + NADH
-
 ?

Synonyms

Synonyms Comment Organism
IMPDH
-
 Tritrichomonas suis
inosine 5'-monophosphate dehydrogenase
-
 Tritrichomonas suis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Tritrichomonas suis

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.4
-
 NAD+ pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
1.4
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
1.9
-
 NAD+ pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis
1.9
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Tritrichomonas suis

Cofactor

Cofactor Comment Organism Structure
NAD+ NAD+ promotes the nucleophilic attack of Cys319 on IMP, the NAD+ site may be an exploitable target for the design of antimicrobial drugs Tritrichomonas suis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.9
-
 NAD+ pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
6.8
-
 NAD+ pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis