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Literature summary for 3.5.3.6 extracted from

  • Ni, Y.; Schwaneberg, U.; Sun, Z.
    Arginine deiminase, a potential anti-tumor drug (2008), Cancer Lett., 261, 1-11.
    View publication on PubMed
Search for more literature for 3.5.3.6

Activating Compound

Activating Compound Comment Organism Structure
additional information PEG binding does not affect the enzyme activity, but does improve pharmocodynamics and pharmacokinetics Mycoplasma hominis

Application

Application Comment Organism
drug development ADI is a potential anti-tumor drug for the treatment of argine-auxotrophic tumors, e.g. hepatocellular carcinoma and melanoma Homo sapiens
drug development ADI is a potential anti-tumor drug for the treatment of argine-auxotrophic tumors, e.g. hepatocellular carcinoma and melanoma Mycoplasma hominis
drug development ADI is a potential anti-tumor drug for the treatment of argine-auxotrophic tumors, e.g. hepatocellular carcinoma and melanoma Mycoplasmopsis arginini
additional information human serum albumin is an effective fusion partner for chemically modifying the enzyme resulting in a longer half-life in serum of two weeks, human serum albumin is more suitable than PEG, overview Homo sapiens
additional information PEG binding does not affect the enzyme activity, but does improve pharmocodynamics and pharmacokinetics, best at 20 kDa size of PEG, overview Mycoplasma hominis
pharmacology ADI is a potential anti-angiogenic agent and is effective in the treatment of leukemia, ADI in clinical studies, overview Homo sapiens
pharmacology ADI is a potential anti-angiogenic agent and is effective in the treatment of leukemia, ADI in clinical studies, overview Mycoplasma hominis
pharmacology ADI is a potential anti-angiogenic agent and is effective in the treatment of leukemia, ADI in clinical studies, overview Mycoplasmopsis arginini

Cloned(Commentary)

Cloned (Comment) Organism
DNA and amino acid sequence determination and analysis, overexpression in Escherichia coli in cytosplasmic inclusion bodies Mycoplasmopsis arginini
DNA and amino acid sequence determination and anaylsis, expression in Escherichia coli Streptococcus sanguinis
expression in Escherichia coli strain BL21 Lactococcus lactis ssp. lactis
expression in Escherichia coli strain BL21(DE3) Pseudomonas aeruginosa
expression in Escherichia coli strain BL21(DE3) Pseudomonas plecoglossicida
expression of His-tagged in Escherichia coli Giardia intestinalis

Crystallization (Commentary)

Crystallization (Comment) Organism
-
 Pseudomonas putida
crystal structure determination and analysis of purified recombinant enzyme at 1.6 and 2.0 A resolution, respectively Mycoplasmopsis arginini
crystal structure determination and analysis of purified recombinant enzyme at 2.45 A resolution, recombinant selenomethionine-labeled enzyme by sitting drop vaour diffusion method Pseudomonas aeruginosa

Protein Variants

Protein Variants Comment Organism
additional information replacement of substrate binding residues leads to highly reduced activity of the mutant enzymes Pseudomonas aeruginosa

Inhibitors

Inhibitors Comment Organism Structure
additional information PEG binding does not affect the enzyme activity, but does improve pharmocodynamics and pharmacokinetics Mycoplasma hominis
PEG modifiying ADI with PEG leads to reduced activity of the complex of 400 kDa MW Mycoplasmopsis arginini

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information kinetics of wild-type and mutant enzymes through molecular dynamics and density functional studies Pseudomonas aeruginosa

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
90000
-
-
 Mycoplasmopsis arginini
96000
-
-
 Mycoplasma hominis
105000
-
-
 Halobacterium salinarum
120000
-
 about, sequence calculation Pseudomonas putida
124000
-
-
 Giardia intestinalis
140000
-
 native enzyme Lactococcus lactis ssp. lactis
184000
-
-
 Pseudomonas aeruginosa

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-arginine + H2O Giardia intestinalis first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Pseudomonas aeruginosa first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Pseudomonas putida first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Halobacterium salinarum first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Streptococcus sanguinis first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Mycoplasma hominis first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Mycoplasmopsis arginini first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Lactococcus lactis ssp. lactis first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Pseudomonas plecoglossicida first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
L-arginine + H2O Homo sapiens first step of the arginine deiminase pathway, overview, ADI is a potential anti-angiogenic agent and is effective in the treatment of leukemia L-citrulline + NH3
-
 ?
L-arginine + H2O Pseudomonas plecoglossicida CGMCC 2039 first step of the arginine deiminase pathway, overview L-citrulline + NH3
-
 ?
additional information Mycoplasmopsis arginini native and recombinant enzyme shows anti-angiogenic and anti-tumor activity inhibiting growth of several murine and human tumor cell lines in vitro and in vivo, e.g. against human umbilical vein cells, HUVEC ?
-
 ?
additional information Pseudomonas putida the enzyme shows anti-tumor activity in murine leukemia lymphoblasts in vitro ?
-
 ?
additional information Mycoplasma hominis the enzyme shows anti-tumor activity inhibiting growth of several murine and human tumor cell lines in vitro and in vivo ?
-
 ?
additional information Pseudomonas plecoglossicida the recombinant enzyme shows anti-tumor activity inhibiting growth of human Hep-G2 tumor cell line ?
-
 ?
additional information Pseudomonas plecoglossicida CGMCC 2039 the recombinant enzyme shows anti-tumor activity inhibiting growth of human Hep-G2 tumor cell line ?
-
 ?

Organism

Organism UniProt Comment Textmining
Giardia intestinalis
-
-
-
Halobacterium salinarum
-
-
-
Homo sapiens
-
-
-
Lactococcus lactis ssp. lactis
-
 strain ATCC 7962
-
Mycoplasma hominis
-
-
-
Mycoplasmopsis arginini
-
-
-
Pseudomonas aeruginosa
-
-
-
Pseudomonas plecoglossicida A7LKB0 isolated from soil
-
Pseudomonas plecoglossicida CGMCC 2039 A7LKB0 isolated from soil
-
Pseudomonas putida
-
-
-
Streptococcus sanguinis
-
-
-

Purification (Commentary)

Purification (Comment) Organism
-
 Halobacterium salinarum
-
 Mycoplasma hominis
native enzyme, and recombinant enzyme from Escherichia coli Mycoplasmopsis arginini
native enzyme, and recombinant enzyme from Escherichia coli strain BL21(DE3), recombinant selenomethionine-labeled enzyme Pseudomonas aeruginosa
native enzyme, and recombinant His-tagged enzyme from Escherichia coli by metal chelating affinity chromatography in a single step Giardia intestinalis
native enzyme, multistep procedure, to homogeneity Pseudomonas putida
recombinant enzyme from Escherichia coli Streptococcus sanguinis
recombinant enzyme from Escherichia coli strain BL21 by anion exchange chromatography and gel filtration Lactococcus lactis ssp. lactis

Reaction

Reaction Comment Organism Reaction ID
L-arginine + H2O = L-citrulline + NH3 the catalytic triad is formed by Cys398, His269, and Glu213, active site and substrate binding structure, six-step reaction mechanism with two key reaction intermediates, Cys398 is responsible for the nucleophilic attack, His269 is the proton acceptor Mycoplasmopsis arginini
a
L-arginine + H2O = L-citrulline + NH3 the catalytic triad is formed by Cys406, His278, and Glu224, active site and substrate binding structure, reaction mechanism with Cys406 being the key residue for the nucleophilic attack, and His278 as general base in the proton transfer chain Pseudomonas aeruginosa
a

Renatured (Commentary)

Renatured (Comment) Organism
recombinant enzyme from Escherichia coli inclusion bodies, refolding by guanidine treatment Mycoplasmopsis arginini

Source Tissue

Source Tissue Comment Organism Textmining
leukemia cell lymphatic Homo sapiens
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
0.115
-
 purifed recombinant enzyme Streptococcus sanguinis
0.476
-
 crude enzyme extract, IU/mg dry cell weight Pseudomonas plecoglossicida
5.4
-
 purified enzyme Halobacterium salinarum
25.5
-
 PEG-modified enzyme Mycoplasmopsis arginini
32.7 37 purified recombinant enzyme Mycoplasmopsis arginini
35
-
 purified enzyme Mycoplasma hominis
36.5
-
 purified recombinant enzyme Giardia intestinalis
41
-
 purified native enzyme Giardia intestinalis
44.5
-
 purified native enzyme Mycoplasmopsis arginini
58.8
-
 purified enzyme Pseudomonas putida
140.3
-
 purified recombinant enzyme Lactococcus lactis ssp. lactis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-arginine + H2O
-
 Homo sapiens L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Giardia intestinalis L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Pseudomonas aeruginosa L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Pseudomonas putida L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Halobacterium salinarum L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Streptococcus sanguinis L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Mycoplasma hominis L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Mycoplasmopsis arginini L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Lactococcus lactis ssp. lactis L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Pseudomonas plecoglossicida L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Giardia intestinalis L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Pseudomonas aeruginosa L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Pseudomonas putida L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Halobacterium salinarum L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Streptococcus sanguinis L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Mycoplasma hominis L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Mycoplasmopsis arginini L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Lactococcus lactis ssp. lactis L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Pseudomonas plecoglossicida L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview, ADI is a potential anti-angiogenic agent and is effective in the treatment of leukemia Homo sapiens L-citrulline + NH3
-
 ?
L-arginine + H2O
-
 Pseudomonas plecoglossicida CGMCC 2039 L-citrulline + NH3
-
 ?
L-arginine + H2O first step of the arginine deiminase pathway, overview Pseudomonas plecoglossicida CGMCC 2039 L-citrulline + NH3
-
 ?
additional information native and recombinant enzyme shows anti-angiogenic and anti-tumor activity inhibiting growth of several murine and human tumor cell lines in vitro and in vivo, e.g. against human umbilical vein cells, HUVEC Mycoplasmopsis arginini ?
-
 ?
additional information the enzyme shows anti-tumor activity in murine leukemia lymphoblasts in vitro Pseudomonas putida ?
-
 ?
additional information the enzyme shows anti-tumor activity inhibiting growth of several murine and human tumor cell lines in vitro and in vivo Mycoplasma hominis ?
-
 ?
additional information the recombinant enzyme shows anti-tumor activity inhibiting growth of human Hep-G2 tumor cell line Pseudomonas plecoglossicida ?
-
 ?
additional information the recombinant enzyme shows anti-tumor activity inhibiting growth of human Hep-G2 tumor cell line Pseudomonas plecoglossicida CGMCC 2039 ?
-
 ?

Subunits

Subunits Comment Organism
dimer
-
 Pseudomonas putida
dimer homodimer Giardia intestinalis
dimer homodimer Halobacterium salinarum
dimer homodimer Mycoplasma hominis
dimer 2 x 48000, recombinant enzyme, SDS-PAGE Mycoplasmopsis arginini
tetramer alphabetagammadelta heterotetramer, a 5fold betabetaalphabeta subunit in symmetrical barrel arrangement and an additional alpha-helix inserted between two betabetaalphabeta subunits Pseudomonas aeruginosa
trimer homotrimer Lactococcus lactis ssp. lactis

Synonyms

Synonyms Comment Organism
ADI
-
 Homo sapiens
ADI
-
 Giardia intestinalis
ADI
-
 Pseudomonas aeruginosa
ADI
-
 Pseudomonas putida
ADI
-
 Halobacterium salinarum
ADI
-
 Streptococcus sanguinis
ADI
-
 Mycoplasma hominis
ADI
-
 Mycoplasmopsis arginini
ADI
-
 Pseudomonas plecoglossicida
LADI
-
 Lactococcus lactis ssp. lactis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
5.6
-
-
 Pseudomonas aeruginosa
6
-
-
 Pseudomonas putida
6
-
-
 Mycoplasma hominis
6.5
-
-
 Mycoplasmopsis arginini
6.5
-
-
 Pseudomonas plecoglossicida
7.2
-
-
 Lactococcus lactis ssp. lactis
7.6
-
-
 Halobacterium salinarum

pH Range

pH Minimum pH Maximum Comment Organism
5 7.5 maximal activity at pH 6.0, 50% of maximal activity at pH 7.0, 10% at pH 7.5 Mycoplasma hominis
5 7.5 maximal activity at pH 6.5, 50% of maximal activity at pH 7.0, 15% at pH 7.5 Pseudomonas plecoglossicida