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Literature summary for 1.1.1.205 extracted from

  • Koehler, G.A.; Gong, X.; Bentink, S.; Theiss, S.; Pagani, G.M.; Agabian, N.; Hedstrom, L.
    The functional basis of mycophenolic acid resistance in Candida albicans IMP dehydrogenase (2005), J. Biol. Chem., 280, 11295-11302.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
gene IMH3, DNA sequence determination of wild-type and mutant IMH3, expression in enzyme-deficient Escherichia coli strain H712, subcloning in Escherichia coli strain DH5alpha Candida albicans

Protein Variants

Protein Variants Comment Organism
A251T the mutation affects the enzyme structure so that the mutant shows altered sensitivity to inhibitors compared to the wild-type enzyme Candida albicans

Inhibitors

Inhibitors Comment Organism Structure
ADP multiple inhibition with tiazofurin, competitive versus NAD+ Candida albicans
mizoribine 5'-phosphate competitive versus NAD+, slow tight-binding, the mutant A251T is 20fold more sesitive Candida albicans
Mycophenolic acid inhibition of the wild-type enzyme uncompetitively versus NAD+, the mutant A251T enzyme is 4fold more resistant to mycophenolic acid Candida albicans
tiazofurin multiple inhibition with ADP, noncompetitive versus NAD+ Candida albicans

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
inosine 5'-phosphate + NAD+ + H2O Candida albicans
-
xanthosine 5'-phosphate + NADH
-
r
inosine 5'-phosphate + NAD+ + H2O Candida albicans CAI-4
-
xanthosine 5'-phosphate + NADH
-
r

Organism

Organism UniProt Comment Textmining
Candida albicans Q59Q46 strain CAI4, gene IMH3
-
Candida albicans CAI-4 Q59Q46 strain CAI4, gene IMH3
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme from wild-type and mutant enzyme-deficient Escherichia coli strain H712 Candida albicans

Reaction

Reaction Comment Organism Reaction ID
IMP + NAD+ + H2O = XMP + NADH + H+ reaction mechanism Candida albicans

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
inosine 5'-phosphate + NAD+ + H2O
-
Candida albicans xanthosine 5'-phosphate + NADH
-
r
inosine 5'-phosphate + NAD+ + H2O
-
Candida albicans CAI-4 xanthosine 5'-phosphate + NADH
-
r

Synonyms

Synonyms Comment Organism
IMPDH
-
Candida albicans

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Candida albicans

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Candida albicans

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Candida albicans
NADH
-
Candida albicans

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetics, structure-inhibitory potency relationship, overview Candida albicans
0.00000001
-
mizoribine 5'-phosphate pH 8.0, 25°C, recombinant mutant A251T Candida albicans
0.0000002
-
mizoribine 5'-phosphate pH 8.0, 25°C, recombinant wild-type enzyme Candida albicans
0.0000011
-
Mycophenolic acid pH 8.0, 25°C, recombinant wild-type enzyme Candida albicans
0.0000044
-
Mycophenolic acid pH 8.0, 25°C, recombinant mutant A251T Candida albicans
16
-
ADP pH 8.0, 25°C, recombinant mutant A251T Candida albicans
26
-
tiazofurin pH 8.0, 25°C, recombinant wild-type enzyme Candida albicans
34
-
ADP pH 8.0, 25°C, recombinant wild-type enzyme Candida albicans
40
-
tiazofurin pH 8.0, 25°C, recombinant mutant A251T Candida albicans