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Literature summary 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

Application

EC Number Application Comment Organism
1.1.1.205 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)

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

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.1.1.205 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

EC Number Inhibitors Comment Organism Structure
1.1.1.205 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
1.1.1.205 additional information structural basis of the drug selectivity, overview Tritrichomonas suis
1.1.1.205 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
1.1.1.205 NAD+
-
 Tritrichomonas suis
1.1.1.205 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]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.205 0.0017
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis
1.1.1.205 0.0024
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant alphabeta core domain, in absence of 100 mM KCl Tritrichomonas suis
1.1.1.205 0.0026
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant full-length enzyme, in absence of 100 mM KCl Tritrichomonas suis
1.1.1.205 0.003
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
1.1.1.205 0.11
-
 NAD+ pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
1.1.1.205 0.15
-
 NAD+ pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis
1.1.1.205 1.1
-
 NAD+ pH 8.0, 25°C, recombinant full-length enzyme, in absence of 100 mM KCl Tritrichomonas suis
1.1.1.205 1.2
-
 NAD+ pH 8.0, 25°C, recombinant alphabeta core domain, in absence of 100 mM KCl Tritrichomonas suis

Metals/Ions

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

Natural Substrates/ Products (Substrates)

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

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.205 Tritrichomonas suis
-
-
-

Purification (Commentary)

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

Reaction

EC Number Reaction Comment Organism Reaction ID
1.1.1.205 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)

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

Synonyms

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

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.1.1.205 25
-
 assay at Tritrichomonas suis

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.1.1.205 1.4
-
 NAD+ pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
1.1.1.205 1.4
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
1.1.1.205 1.9
-
 NAD+ pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis
1.1.1.205 1.9
-
 inosine 5'-phosphate pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.1.1.205 8
-
 assay at Tritrichomonas suis

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.205 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]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.1.1.205 2.9
-
 NAD+ pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl Tritrichomonas suis
1.1.1.205 6.8
-
 NAD+ pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl Tritrichomonas suis