1.1.1.205: IMP dehydrogenase
This is an abbreviated version!
For detailed information about IMP dehydrogenase, go to the full flat file.
Word Map on EC 1.1.1.205
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1.1.1.205
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mycophenolic
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purine
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guanine
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mofetil
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ribavirin
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leukemia
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tiazofurin
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rejection
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xmp
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pharmacodynamic
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salvage
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hypoxanthine
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cyclosporine
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allograft
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prodrugs
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mizoribine
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phosphoribosyltransferase
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ribonucleotide
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xanthosine
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guanylate
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tad
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calcineurin
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dgtp
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adenylosuccinate
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6-mercaptopurine
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dihydrofolate
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hypoxanthine-guanine
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cryptosporidium
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tacrolimus
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thiopurine
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riboside
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azathioprine
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glucuronide
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parvum
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benzamide
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pigmentosa
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sirolimus
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6-thioguanine
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analysis
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rbv
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amido
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cryptosporidiosis
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c-nucleoside
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tritrichomonas
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enteric-coated
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predose
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hgprt
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pharmacology
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diagnostics
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drug development
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medicine
- 1.1.1.205
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mycophenolic
- purine
- guanine
- mofetil
- ribavirin
- leukemia
- tiazofurin
-
rejection
- xmp
-
pharmacodynamic
-
salvage
- hypoxanthine
-
cyclosporine
-
allograft
-
prodrugs
- mizoribine
- phosphoribosyltransferase
- ribonucleotide
- xanthosine
-
guanylate
- tad
- calcineurin
- dgtp
- adenylosuccinate
- 6-mercaptopurine
- dihydrofolate
-
hypoxanthine-guanine
- cryptosporidium
- tacrolimus
- thiopurine
- riboside
- azathioprine
- glucuronide
- parvum
- benzamide
- pigmentosa
- sirolimus
- 6-thioguanine
- analysis
- rbv
-
amido
- cryptosporidiosis
-
c-nucleoside
- tritrichomonas
-
enteric-coated
-
predose
- hgprt
- pharmacology
- diagnostics
- drug development
- medicine
Reaction
Synonyms
A1S_3321, BTH_I2056, class I IMPDH, class II IMPDH, dehydrogenase, inosinate, DR63_268, EC 1.2.1.14, GBAA_0008, guaB, 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, IMPDHA, IMPDHab, IMPDHba, IMPDHbt, IMPDHI, IMPDHII, IMPDHkp, IMPDHlpp, IMPDHnm, IMPDHpa, 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 2, inosine 5-monophosphate dehydrogenase type I, inosine 5’ -monophosphate dehydrogenase, inosine 5’-monophosphate dehydrogenase 2, inosine monophosphate dehydrogenase, inosine monophosphate dehydrogenase-1, inosine monophosphate dehydrogenase-2, inosine monophosphate oxidoreductase, inosine-5'-monophosphate dehydrogenase, inosine-5'-phosphate dehydrogenase, inosine-5-monophosphate dehydrogenase, inosinic acid 5’-monophosphate dehydrogenase, inosinic acid dehydrogenase, lpg1723, mpaF, NMC1103, Raspberry protein, Rv3411c, SOI12, Superoxide-inducible protein 12, type 1 inosine monophosphate, type 2 inosine monophosphate dehydrogenase
ECTree
1.1.1.205 IMP dehydrogenaseAdvanced search results
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results (Engineering
Engineering on EC 1.1.1.205 - IMP dehydrogenase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
K481E
site-directed mutagenesis, site 481 is a key mutation site to affect the NAD+ affinity, which accounts for the higher catalytic efficiency of the IMPDH mutant compared to the wild-type enzyme
P166S
site-directed mutagenesis, the mutant shows unaltered catalytic activity compared to the wild-type enzyme
K481E
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site-directed mutagenesis, site 481 is a key mutation site to affect the NAD+ affinity, which accounts for the higher catalytic efficiency of the IMPDH mutant compared to the wild-type enzyme
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P166S
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site-directed mutagenesis, the mutant shows unaltered catalytic activity compared to the wild-type enzyme
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A251T
C305A
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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
D338A
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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
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is inhibited 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+
S250A/L444Y
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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
C331A
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mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
D226N
D364A
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mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
G326A
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mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
H372P
IMPDH1 polymorphism, which is associated with retinal degeneration
K238E
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
L227P
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
L263F
N198K
Q441E
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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
R224P
R231P
R322K
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less than 0.045% of wild type activity, therefore no further characterization possible
R322K/Q441E
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less than 0.045% of wild type activity, therefore no further characterization possible
S329A
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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
V268I
Y12A
the mutation abrogates polymerization of the enzyme. Mutant enzymes remain as monodisperse tetramers in solution
Y487C
S267A
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the mutant enzyme of isoform IMPDHA is inhibited by mycophenolic acid
C319S
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is essentially inactive, two-step binding process for inosine 5'-phosphate remains
DELTA(101-226)
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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
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substitution increases the equilibrium constant for the dehydrogenase step but decreases the equilibrium between open and closed conformations of a mobile flap
K230E/R231E
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site-directed mutagenesis, the exchange in the subdomain leads to 20fold reduced affinity for nucleic acids
K310R
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10fold decrease of Ki for mycophenolic acid, increase of Km for IMP and NAD+
Q324A
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substitution increases the equilibrium constant for the dehydrogenase step but decreases the equilibrium between open and closed conformations of a mobile flap
R212E/R217E
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site-directed mutagenesis, the exchange in the subdomain leads to 20fold reduced affinity for nucleic acids
R322A
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substitution increases the equilibrium constant for the dehydrogenase step but decreases the equilibrium between open and closed conformations of a mobile flap
R322E
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substitution decreases the rates of hydride transfer and hydrolysis by factors of 2000 and 130, respectively
R418A
R418A/Y419F
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site-directed mutagenesis, altered kinetics compared to the wild-type enzyme, no rescue of the mutant by aminoguanidine, overview
R418H
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site-directed mutagenesis, altered kinetics compared to the wild-type enzyme
R418K
R418Q
T312A
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site-directed mutagenesis, altered kinetics compared to the wild-type enzyme
Y419F
additional information
A251T
the mutation affects the enzyme structure so that the mutant shows altered sensitivity to inhibitors compared to the wild-type enzyme
A251T
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is 4fold less sensitive to mycophenolic acid but 40fold more sensitve to mizoribine monophosphate. Mutation does not affect kcat but decreases Km values for both substrates, is catalytically more efficient. Mutation renders the enzyme resistant to NAD+ substrate inhibition, stabilizes the closed conformation, which has opposing effects on enzyme susceptiblities to mycophenolic acid and mizoribine monophosphate
A251T
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the mutation affects the enzyme structure so that the mutant shows altered sensitivity to inhibitors compared to the wild-type enzyme
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D226N
naturally occuring mutation causing autosomal dominant retinitis pigmentosa, site-directed mutagenesis of IMPDH1, similar activity and protein stability compared to the wild-type enzyme
D226N
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mutant of isoform IMPDH1(546), and mutant of isoform IMPDH1(595), both are localized to cytosol and exhibit kinetic parameters identical to wild-type
D226N
IMPDH1 polymorphism, which is associated with retinal degeneration
D226N
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
L263F
IMPDH2 polymorphism, which decreases the value of kcat by a factor of 10
N198K
IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis
N198K
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
R224P
naturally occuring mutation causing autosomal dominant retinitis pigmentosa, site-directed mutagenesis of IMPDH1, the mutant shows altered subcellular localization compared to the wild-type enzyme, similar activity and protein stability compared to the wild-type enzyme
R224P
IMPDH1 polymorphism, which is associated with retinal degeneration
R224P
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
R231P
IMPDH1 polymorphism, which causes autosomal dominant retinitis pigmentosa
R231P
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
V268I
site-directed mutagenesis of IMPDH1, pathogenic mutation, the mutant shows altered subcellular localization compared to the wild-type enzyme, similar activity and protein stability compared to the wild-type enzyme
V268I
IMPDH1 polymorphism, which is associated with retinal degeneration
R418A
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site-directed mutagenesis, altered kinetics compared to the wild-type enzyme, chemical rescue of the mutant by guanidine, methylguanidine, ethylguanidine, acteamide, and aminoguanidine, not by hydroxyurea, overview
R418A
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site-directed mutagenesis, chemical rescue of the mutant by guanidine, methylguanidine, ethylguanidine, acteamide, and aminoguanidine, not by hydroxyurea, overview
R418A
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decreases steady-state enzymic activity 500fold but presteady burst of NADH production in the first enzyme turnover is unaffected nor is the rate NADH release. Guanidine derivates rescue the mutation, which is attributed to an acceleration of the E-XMP hydrolysis
R418K
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site-directed mutagenesis, altered kinetics compared to the wild-type enzyme
R418K
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does not impair E-XMP hydrolysis but destabilizes the closed conformation, resulting in a strong enzyme inhibition by NAD and NADH
R418Q
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site-directed mutagenesis, altered kinetics compared to the wild-type enzyme
R418Q
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stabilizes the closed conformation but it is defective in E-XMP hydrolysis
Y419F
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site-directed mutagenesis, altered kinetics compared to the wild-type enzyme
Y419F
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decreases steady-state enzymic activity 500fold but presteady burst of NADH production in the first enzyme turnover is unaffected nor is the rate NADH release
additional information
construction of a deletion mutant IMPDHDELTACBS lacking the CBS domains
additional information
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construction of a deletion mutant IMPDHDELTACBS lacking the CBS domains
additional information
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construction of a deletion mutant IMPDHDELTACBS lacking the CBS domains
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additional information
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construction of a short and a long CBS domain deletion mutant variant, BaIMPDHDELTAS and BaIMPDHDELTAL. Deletion of residues Val95-Thr200 and Glu92-Arg220, respectively
additional information
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construction of a short CBS domain deletion mutant variant, CjIMPDHDELTAS. Deletion of residues Val92-Thr195
additional information
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construction of a long CBS domain deletion mutant variant, ClpIMPDHDELTAL. Deletion of residues Gln89-Arg215
additional information
construction of the catalytically active AgIMPDH-DELTABateman enzyme mutant, that has a the deletion of the regulatory domain facilitating crystallization
additional information
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construction of the catalytically active AgIMPDH-DELTABateman enzyme mutant, that has a the deletion of the regulatory domain facilitating crystallization
additional information
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construction of the catalytically active AgIMPDH-DELTABateman enzyme mutant, that has a the deletion of the regulatory domain facilitating crystallization
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additional information
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construction of guanine-prototrophic strain by deletion of the cystathione beta-synthase domain from the chromosomal gene of inosine 5'-monophosphate dehydrogenase. Mutant strain exhibits a substantially elevated ATP content and a slightly reduced GTP content. Activities of inosine 5'-monophosphate dehydrogenase, adenylosuccinate synthetase and GMP reductase are two- to threefold lower than in wild-type
additional information
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deletion of the Bateman domain has no effect on the in vitro IMPDH activity. In vivo deletion of the Bateman domain of IMPDH (guaBDELTACBS) sensitizes the bacterium to growth arrest by adenosine and inosine, thus derepresses the synthesis of AMP from inosine 5'-phosphate. The growth inhibitory effect of inosine can be rescued by second-site suppressor mutations in the genes responsible for the conversion of inosine to AMP (gsk, purA, and purB) as well as by the prsA1 allele, which encodes a 5-phosphoribosyl 1-pyrophosphate synthetase that is insensitive to allosteric inhibition by adenylate nucleotides. The guaBDELTACBS phenotype can be complemented in trans by a mutant guaB allele, which encodes the catalytically disabled IMPDH C305A protein containing an intact Bateman domain
additional information
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construction of umbilical vein endothelial cell IMPDH-1 knockout lines
additional information
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identification of nine genetic variants in type II enzyme
additional information
deletion of IMPDH CBS domain of MtbIMPDH2, residues E126-R252 are replaced with a GG linker. The MtbIMPDH2DELTACBS mutant shows significantly improved solubility and crystallizability properties compared to the wild-type enzyme, with the steady state kinetic parameters comparable to those reported for the wild-type enzyme
additional information
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deletion of IMPDH CBS domain of MtbIMPDH2, residues E126-R252 are replaced with a GG linker. The MtbIMPDH2DELTACBS mutant shows significantly improved solubility and crystallizability properties compared to the wild-type enzyme, with the steady state kinetic parameters comparable to those reported for the wild-type enzyme
additional information
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deletion of IMPDH CBS domain of MtbIMPDH2, residues E126-R252 are replaced with a GG linker. The MtbIMPDH2DELTACBS mutant shows significantly improved solubility and crystallizability properties compared to the wild-type enzyme, with the steady state kinetic parameters comparable to those reported for the wild-type enzyme
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additional information
construction of a mutant lacking the CBS domains, IMPDH mutant DELTACBS. The DELTACBS variant lacks the CBS motifs from Ala92 to Lys202 of the full-length enzyme. This variant is fully active and its kinetic parameters are similar to those of wild-type IMPDHpa in the presence of its positive effector Mg-ATP. The catalytic activity of the D199N variant is still sensitive to Mg-ATP, influencing both the maximal rate and the affinity for IMP, but the cooperativity effect for IMP is lost
additional information
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construction of a mutant lacking the CBS domains, IMPDH mutant DELTACBS. The DELTACBS variant lacks the CBS motifs from Ala92 to Lys202 of the full-length enzyme. This variant is fully active and its kinetic parameters are similar to those of wild-type IMPDHpa in the presence of its positive effector Mg-ATP. The catalytic activity of the D199N variant is still sensitive to Mg-ATP, influencing both the maximal rate and the affinity for IMP, but the cooperativity effect for IMP is lost
additional information
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impdh-knockout mutant (DELTAIMPDH) is slower in growth and one pH unit higher than the parent after 6 h of culturing. DELTAIMPDH is negative for fermentation maltose, salicin, lactose, raffinose, mannose and glucose metabolism in contrast to the parent strain, but it can fermentate esculin, nitrate and glucosamine like the parent. The mutant is attenuated in mouse models of infection for 2.5times and not be capable of causing death in porcine models of infection in contrast with the parent
additional information
construction of an IMPDH knockout mutant strain ZY05719
additional information
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impdh-knockout mutant (DELTAIMPDH) is slower in growth and one pH unit higher than the parent after 6 h of culturing. DELTAIMPDH is negative for fermentation maltose, salicin, lactose, raffinose, mannose and glucose metabolism in contrast to the parent strain, but it can fermentate esculin, nitrate and glucosamine like the parent. The mutant is attenuated in mouse models of infection for 2.5times and not be capable of causing death in porcine models of infection in contrast with the parent
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additional information
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construction of an IMPDH knockout mutant strain ZY05719
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additional information
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construction of a long CBS domain deletion mutant variant, VcIMPDHDELTAL. Deletion of residues Phe91-Arg219
