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Literature summary for 1.1.1.205 extracted from

  • Rostirolla, D.; Milech De Assuncao, T.; Bizarro, C.; Basso, L.; Santos, D.
    Biochemical characterization of Mycobacterium tuberculosis IMP dehydrogenase: kinetic mechanism, metal activation and evidence of a cooperative system (2014), RSC Adv., 4, 26271-26287.
No PubMed abstract available

Application

Application Comment Organism
drug development IMPDH from Mycobacterium tuberculosis (MtIMPDH) is a potential molecular target to inhibitor development Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
gene guaB2, recombinant expression in Escherichia coli strain C41(DE3) Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
APAD+ substrate inhibition, uncompetitive substrate inhibition versus IMP Mycobacterium tuberculosis
additional information several inhibitors compete with the flap for the vacant NADH site, thus preventing the hydrolysis of E-XMP* reaction intermediate Mycobacterium tuberculosis
NAD+ substrate inhibition Mycobacterium tuberculosis
NADH product inhibition, noncompetitive versus IMP, NAD+, and K+ Mycobacterium tuberculosis
XMP product inhibition, competitive versus IMP, noncompetitive versus NAD+ and K+ Mycobacterium tuberculosis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information steady-state kinetics and kinetic analysis, detailed overview Mycobacterium tuberculosis
0.887
-
NAD+ recombinant enzyme, pH 8.5, 37°C Mycobacterium tuberculosis

Metals/Ions

Metals/Ions Comment Organism Structure
K+ required, activates, the enzyme contains one K+ per subunit Mycobacterium tuberculosis
additional information the enzyme activity is dependent on the presence of a monovalent cation, preferaby K+. Neither Na+ nor Li+, which have lower ionic radii than K+, activate the MtIMPDH. Divalent cations, such as Mg2+ and Ca2+, do not activate the enzyme even at 200 mM Mycobacterium tuberculosis

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
54775
-
-
Mycobacterium tuberculosis
220000
-
about, molecular weight determination by cross-linking experiments and 12% SDS-PAGE analysis, since the enzyme elutes as different species depending on its concentration, indicating the presence of different aggregated forms Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
IMP + NAD+ + H2O Mycobacterium tuberculosis
-
XMP + NADH + H+
-
?
IMP + NAD+ + H2O Mycobacterium tuberculosis H37Rv
-
XMP + NADH + H+
-
?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WKI7
-
-
Mycobacterium tuberculosis H37Rv P9WKI7
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant soluble enzyme 1.7fold from Escherichia coli strain C41(DE3) by affinity chromatography and gel filtration Mycobacterium tuberculosis

Reaction

Reaction Comment Organism Reaction ID
IMP + NAD+ + H2O = XMP + NADH + H+ a steady-state ordered Bi Bi kinetic mechanism in which IMP binds first followed by NAD+, and product release is ordered. Hydride transfer appears not to be rate-limiting. The pH-rate profile indicates one deprotonated group essential for catalysis Mycobacterium tuberculosis

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
2
-
purified recombinant enzyme, pH 8.5, 37°C Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
IMP + APAD+ + H2O
-
Mycobacterium tuberculosis XMP + APADH + H+
-
?
IMP + APAD+ + H2O
-
Mycobacterium tuberculosis H37Rv XMP + APADH + H+
-
?
IMP + NAD+ + H2O
-
Mycobacterium tuberculosis XMP + NADH + H+
-
?
IMP + NAD+ + H2O
-
Mycobacterium tuberculosis H37Rv XMP + NADH + H+
-
?

Subunits

Subunits Comment Organism
More MtIMPDH predominates as a tetramer Mycobacterium tuberculosis
tetramer 4 * 54775, mass spectrometry, x * 55000, recombinnat enzyme, SDS-PAGE, 4 * 54700, about, sequence calculation Mycobacterium tuberculosis

Synonyms

Synonyms Comment Organism
guaB2
-
Mycobacterium tuberculosis
IMP dehydrogenase
-
Mycobacterium tuberculosis
IMPDH
-
Mycobacterium tuberculosis
inosine 5'-monophosphate dehydrogenase
-
Mycobacterium tuberculosis
Rv3411c
-
Mycobacterium tuberculosis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Mycobacterium tuberculosis

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.1
-
NAD+ recombinant enzyme, pH 8.5, 37°C Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8 8.5
-
Mycobacterium tuberculosis

pH Range

pH Minimum pH Maximum Comment Organism
7 10 activity range, profile overview Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
3-acetylpyridine adenine dinucleotide the NAD+ analog 3-acetylpyridine adenine dinucleotide (APAD+) is a substrate for MtIMPDH and the dependence of velocity on increasing concentrations of APAD+ (Fig. 4B) also displayed substrate inhibition Mycobacterium tuberculosis
NAD+ groups with pK values of 7.5 and 9.0 are important for NAD+ binding Mycobacterium tuberculosis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetic analysis, detailed overview Mycobacterium tuberculosis
6.3
-
NAD+ recombinant enzyme, pH 8.5, 37°C Mycobacterium tuberculosis

General Information

General Information Comment Organism
malfunction inhibition of IMPDH causes an overall reduction in guanine nucleotide pools and, as phosphoribosyl pyrophosphate (PRPP) synthetase and ribonucleotide reductase are allosterically regulated by these nucleotides, it may affect several metabolic pathways Mycobacterium tuberculosis