1.1.1.205: IMP dehydrogenase

This is an abbreviated version, for detailed information about IMP dehydrogenase, go to the full flat file.

Reaction

IMP
+
NAD+
+
H2O
=
XMP
+
NADH
+
H+

Synonyms

dehydrogenase, inosinate, EC 1.2.1.14, guaB2, IMD2, IMD3, IMD4, IMP dehydrogenase, IMP DH, IMP oxidoreductase, IMP-DH, IMP:NAD oxidoreductase, IMP:NAD+ oxidoreductase, IMPD, IMPDH, IMPDH II, IMPDH-1, IMPDH-B, IMPDH-S, IMPDH1, IMPDH2, inosinate dehydrogenase, inosine 5' monophosphate dehydrogenase, inosine 5'-monophosphate dehydrogenase, inosine 5'-monophosphate dehydrogenase 2, inosine 5'-phosphate dehydrogenase, inosine 5-monophosphate dehydrogenase, inosine 5-monophosphate dehydrogenase type I, inosine 5’ -monophosphate dehydrogenase, inosine monophosphate dehydrogenase, inosine monophosphate oxidoreductase, inosine-5'-monophosphate dehydrogenase, inosine-5'-phosphate dehydrogenase, inosinic acid 5’-monophosphate dehydrogenase, inosinic acid dehydrogenase, mpaF, Raspberry protein, SOI12, Superoxide-inducible protein 12, type 1 inosine monophosphate, type 2 inosine monophosphate dehydrogenase

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.205 IMP dehydrogenase

Engineering

Engineering on EC 1.1.1.205 - IMP dehydrogenase

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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C305A
-
the guaBDELTACBS phenotype can be complemented in trans by a mutant guaB allele, which encodes the catalytically disabled IMPDHC305A protein containing an intact Bateman domain
D13A
-
is activated by Mg2+ and Ca2+ in lieu of K+
D248A
-
selectively impairs NAD binding
D338A
-
affects Kcat more than 600fold and increases the Km for inosine 5'-phosphate, hydride transfer rate is diminished at least 5000fold, rate of inactivation by 6-chloroinosine 5'-phosphate is increased 3fold
D50A
-
is inhibted by Mg2+ and Ca2+, Mg2+ inhibition becomes uncompetitive with respect to K+ and competitive with both inosine 5'-phosphate and NAD+, in contrast to the wild-type enzyme, the mutant is inactive in the absence of K+
E460A
-
is activated by Mg2+ and Ca2+ in lieu of K+
S250A/L444Y
-
mutation of residues corresponding to structural motif A250/Y358 of Cryptosporidium parvum. Mutation renders the enzyme susceptible to inhibitors
A285T
site-directed mutagenesis of IMPDH1, similar activity and protein stability compared to the wild-type enzyme
A462T
-
increase in the Ki for mycophenolic acid
C331A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
D301N
-
IMPDH1 polymorphism, which does not affect protein function
D364A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
F465S/N470G
-
increase in the Ki for mycophenolic acid
G324D
-
IMPDH1 polymorphism, which does not affect protein function
G326A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
G519R
-
IMPDH1 polymorphism, which does not affect protein function
H296R
-
IMPDH1 polymorphism, which does not affect protein function
H372P
-
IMPDH1 polymorphism, which is associated with retinal degeneration
K409A
-
mutated type 2 isozyme, low-activity protein with increased Km value
M70A
-
mutated type 2 isozyme, low-activity protein with increased Km value
N198K
-
IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis
Q277R
-
increase in the Ki for mycophenolic acid
Q277R/A462T
-
increase in the Ki for mycophenolic acid
Q441E
-
less than 0.045% of wild type activity, therefore no further characterization possible
R105W
-
IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis
R231P
-
IMPDH1 polymorphism, which causes autosomal dominant retinitis pigmentosa
R322K
-
less than 0.045% of wild type activity, therefore no further characterization possible
R322K/Q441E
-
less than 0.045% of wild type activity, therefore no further characterization possible
S329A
-
mutated type 2 isozyme, increases the Km for both inosine 5'-phosphate and NAD without altering kcat
T116M
-
IMPDH1 polymorphism, which is associated with retinal degeneration
Y111A
-
mutated type 2 isozyme, low-activity protein with increased Km value
E421Q
-
full enzymatic activity
R406A
-
no enzymatic activity
Y450A
-
25% of enzymatic activity
Y450D
-
no enzymatic activity
C319S
-
is essentially inactive, two-step binding process for inosine 5'-phosphate remains
DELTA(101-226)
-
crystallized in complex with inosine 5'-phosphate and inhibitor beta-CH2-tiazofurin adenine dinucletoide, at 2.2 A resolution or in complex with inhibitor mizoribine monophosphate, at 2 A resolution
E323A
-
substitution increases the equilibrium constant for the dehydrogenase step but decreases the equilibrium between open and closed conformations of a mobile flap
E431Q
-
6fold decrease of Ki for mycophenolic acid
K230E/R231E
-
site-directed mutagenesis, the exchange in the subdomain leads to 20fold reduced affinity for nucleic acids
K310R
-
10fold decrease of Ki for mycophenolic acid, increase of Km for IMP and NAD+
K310R/E431Q
-
20fold increase in sensitivity to mycophenolic acid
Q324A
-
substitution increases the equilibrium constant for the dehydrogenase step but decreases the equilibrium between open and closed conformations of a mobile flap
R212E/R217E
-
site-directed mutagenesis, the exchange in the subdomain leads to 20fold reduced affinity for nucleic acids
R322A
-
substitution increases the equilibrium constant for the dehydrogenase step but decreases the equilibrium between open and closed conformations of a mobile flap
R322E
-
substitution decreases the rates of hydride transfer and hydrolysis by factors of 2000 and 130, respectively
R418A/Y419F
-
site-directed mutagenesis, altered kinetics compared to the wild-type enzyme, no rescue of the mutant by aminoguanidine, overview
R418H
-
site-directed mutagenesis, altered kinetics compared to the wild-type enzyme
T312A
-
site-directed mutagenesis, altered kinetics compared to the wild-type enzyme
additional information