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Information on EC 1.1.1.205 - IMP dehydrogenase and Organism(s) Bacillus anthracis and UniProt Accession Q81W29

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     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
IUBMB Comments
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
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This record set is specific for:
Bacillus anthracis
UNIPROT: Q81W29
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Word Map
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The taxonomic range for the selected organisms is: Bacillus anthracis
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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IMP
+
NAD+
+
H2O
=
XMP
+
NADH
+
H+
+
+
=
+
+
Synonyms
impdh, imp dehydrogenase, inosine monophosphate dehydrogenase, impdh2, impdh1, inosine 5'-monophosphate dehydrogenase, inosine-5'-monophosphate dehydrogenase, impdh ii, imp dh, inosinate dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
class II IMPDH
Q81W29
-
GBAA_0008
Q81W29
-
guaB
Q81W29
-
IMPDH
Q81W29
-
IMPDHba
Q81W29
-
inosine-5'-monophosphate dehydrogenase
Q81W29
-
dehydrogenase, inosinate
-
-
-
-
IMP dehydrogenase
IMP oxidoreductase
-
-
-
-
IMPD
-
-
-
-
IMPDH
inosinate dehydrogenase
-
-
-
-
inosine 5'-monophosphate dehydrogenase
inosine monophosphate dehydrogenase
-
-
-
-
inosine monophosphate oxidoreductase
-
-
-
-
inosine-5'-phosphate dehydrogenase
-
-
-
-
inosinic acid dehydrogenase
-
-
-
-
Raspberry protein
-
-
-
-
SOI12
-
-
-
-
Superoxide-inducible protein 12
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
the IMPDH reaction involves two chemical transformations. First, the catalytic Cys attacks IMP, and hydride is transferred to NAD to form the covalent intermediate E-XMP*. In the second step, E-XMP* is hydrolyzed to produce XMP
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
IMP:NAD+ oxidoreductase
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
CAS REGISTRY NUMBER
COMMENTARY hide
9028-93-7
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
IMP + NAD+ + H2O
XMP + NADH + H+
show the reaction diagram
Q81W29
-
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
show the reaction diagram
Q81W29
-
-
-
?
IMP + NAD+ + H2O
XMP + NADH + H+
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
IMP + NAD+ + H2O
XMP + NADH + H+
show the reaction diagram
Q81W29
-
-
-
?
IMP + NAD+ + H2O
XMP + NADH + H+
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
MgATP2-
Q81W29
has a positive effector of IMPDHpa acting on the maximal rate and on the affinity for IMP. The positive effector binds onto the two CBS modules, with consequences on the global shape
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-[(1R)-1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]ethoxy]quinoline 1-oxide
Q81W29
-
Mycophenolic acid
Q81W29
noncompetitive with regard to inosine monophosphate and NAD+
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
Q81W29
-
NAD+
Q81W29
-
xanthosine 5'-phosphate
Q81W29
competitive with regard to inosine monophosphate
(2R)-2-[(naphthalen-1-yl)oxy]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
Q21
2-(1-naphthalenyloxy)-N-[(2-(4-pyridinyl)-5-benzoxazolyl)]-(2S)-propanamide
-
-
2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)-N-(6,7,8,9-tetrahydrodibenzo[b,d]furan-2-yl)acetamide
D67
2-chloro-5-[[(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)carbamoyl]amino]benzamide
P32
2-chloro-N-methyl-5-[[[1-methyl-1-[3-(1-methylethenyl)phenyl]ethyl]amino]carbonyl]aminobenzamide
-
-
3,4-dihydro-3-methyl-4-oxo-N-(6,7,8,9-tetrahydro2-dibenzofuranyl)-1-phthalazineacetamide
-
-
3-(2-[[(4-chlorophenyl)carbamoyl]amino]propan-2-yl)-N-hydroxybenzene-1-carboximidamide
P200
4-[(1R)-1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]ethoxy]quinolin-2(1H)-one
A110
4-[(1R)-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4yl]ethoxy]quinoline-1-oxide
-
-
N-(4-bromophenyl)-N'-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)urea
P68
N-(4-bromophenyl)-N-[(1-methylethenyl)phenyl]ethyl urea
-
-
N-(4-bromophenyl)-N-[1-[3-[1-(hydroxyimino)ethyl]phenyl]-1-methylethyl] urea
-
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
N-[2-chloro-5-[([2-[3-(prop-1-en-2-yl)phenyl]propan-2-yl]carbamoyl)amino]phenyl]-beta-D-xylofuranosylamine
N-[4-chloro-3-(alpha-D-ribofuranosyloxy)phenyl]-N'-[2-[3-(prop-1-en-2-yl)phenyl]propan-2-yl]urea
P178
N-[4-chloro-3-[4-(trifluoromethyl)-1,3-thiazol-2-yl]phenyl]-N'-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)urea
P182
NAD+
-
substrate inhibition
oxanosine monophosphate
additional information
-
inhibitor synthesis and binding structure to the enzyme determined with the CBS deletion mutant enzyme variants, overview
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Cs+
Q81W29
36% of the activity with K+
dimethyl sulfoxide
Q81W29
up to 15-20% increase IMP dehydrogenase activity
K+
Q81W29
optimal activation at 100-150 mM K+
Li+
Q81W29
less than 1% of the activity with K+
MgATP2-
Q81W29
has a positive effector of IMPDHpa acting on the maximal rate and on the affinity for IMP. The positive effector binds onto the two CBS modules, with consequences on the global shape
Na+
Q81W29
less than 1% of the activity with K+
NH4+
Q81W29
77% of the activity with K+
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.12 - 0.148
IMP
0.018
Inosine 5'-diphosphate
Q81W29
pH 8.0, 22°C
0.55 - 2.209
NAD+
0.061 - 0.15
IMP
0.46 - 0.7
NAD+
additional information
additional information
Q81W29
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.4
Inosine 5'-diphosphate
Q81W29
pH 8.0, 22°C
3 - 6.1
IMP
3
NAD+
at pH 8.0 and 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0039 - 0.0048
Mycophenolic acid
3.9
NAD+
Q81W29
pH 8.0, 22°C
0.218
xanthosine 5'-phosphate
Q81W29
pH 8.0, 22°C
0.115
GMP
at pH 8.0 and 25°C
3.8 - 5.3
NAD+
0.00034
oxanosine monophosphate
at pH 8.0 and 25°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000057
4-[(1R)-1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]ethoxy]quinoline 1-oxide
Bacillus anthracis
Q81W29
pH 8.0, 22°C
0.000057
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
Bacillus anthracis
Q81W29
pH 8.0, 22°C
0.000023 - 0.000038
2-(1-naphthalenyloxy)-N-[(2-(4-pyridinyl)-5-benzoxazolyl)]-(2S)-propanamide
0.00001 - 0.000047
2-chloro-N-methyl-5-[[[1-methyl-1-[3-(1-methylethenyl)phenyl]ethyl]amino]carbonyl]aminobenzamide
0.00067 - 0.0008
3,4-dihydro-3-methyl-4-oxo-N-(6,7,8,9-tetrahydro2-dibenzofuranyl)-1-phthalazineacetamide
0.000043 - 0.000137
4-[(1R)-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4yl]ethoxy]quinoline-1-oxide
0.000019 - 0.000065
N-(4-bromophenyl)-N-[(1-methylethenyl)phenyl]ethyl urea
0.000006 - 0.000028
N-(4-bromophenyl)-N-[1-[3-[1-(hydroxyimino)ethyl]phenyl]-1-methylethyl] urea
0.000067 - 0.0001
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.2
Q81W29
-
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
Q81W29
assay at
25
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
Q81W29
classification of bacterial IMPDHs according to the regulation of their catalytic properties and their quaternary structures. Class I IMPDHs are cooperative enzymes for IMP, which are activated by MgATP2- and are octameric in all tested conditions. On the other hand, class II IMPDHs behave as Michaelis-Menten enzymes for both substrates and are tetramers in their apo state or in the presence of IMP, which are shifted to octamers in the presence of NAD+ or MgATP2-
metabolism
Q81W29
the enzyme occupies a key position in purine nucleotide metabolism catalyzing the rate-limiting NAD-dependent oxidation of IMP to XMP
physiological function
Q81W29
IMPDH functional regulation, overview
malfunction
-
the inhibition of IMPDH leads to the depletion of the guanine nucleotide pool, which blocks proliferation
metabolism
-
the enzyme catalyzes the first and rate-limiting step in guanine nucleotide biosynthesis
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer or octamer
Q81W29
in the presence of NAD+, IMPDHba is predominantly octameric
tetramer
-
4 * 40435, long enzyme truncation CBS-mutant BaIMPDHDELTAL, sequence calculation, 4 * 37920, short enzyme truncation CBS-mutant BaIMPDHDELTAL, sequence calculation
additional information
Q81W29
IMPDH shares a two-domain organization composed of one catalytic domain, a (beta/alpha)8 barrel, and a smaller flanking domain, containing two CBS modules, forming together the so-called Bateman domain, model for the quaternary structure modulation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in a phosphate ion-bound form and in complex with its substrate, inosine 5'-monophosphate, and product, xanthosine 5'-monophosphate, to 2.38-2.65 A resolution. The enzyme monomer has a typical two-domain structure, the catalytic domain, which is a TIM barrel, and the CBS domain. In all structures, each monomer contains a ligand bound in the active site, i.e.phosphate anion in the apo structure and IMP and XMP in the substrate and product-bound structures, respectively. In all the structures, the CBS domains are partially disordered
Q81W29
enzyme in complex with oxanosine monophosphate, sitting drop vapor diffusion method, using 0.1 M magnesium chloride, 0.1 M MES, pH 6.5, and 30% (v/v) PEG 400
purified recombinant short enzyme mutant BaIMPDHDELTAS in apoform from 0.2 M sodium chloride, 0.1 M sodium cacodylate, pH 6.5, and 2 M ammonium sulfate, 16°C, and purified recombinant long enzyme mutant BaIMPDHDELTAL in complex with IMP and with inhibitors 4-[(1R)-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4yl]ethoxy]quinoline-1-oxide, ((alpha-methyl-)N-2-naphthalenyl-2-(2-pyridinyl)-1H-benzimidazole-)1-acetamide, 3,4-dihydro-3-methyl-4-oxo-N-(6,7,8,9-tetrahydro2-dibenzofuranyl)-1-phthalazineacetamide, 2-chloro-N-methyl-5-[[[1-methyl-1-[3-(1-methylethenyl)phenyl]ethyl]amino]carbonyl]aminobenzamide, N-(4-bromophenyl)-N-[1-[3-[1-(hydroxyimino)ethyl]phenyl]-1-methylethyl] urea, and 2-(1-naphthalenyloxy)-N-[(2-(4-pyridinyl)-5-benzoxazolyl)]-(2S)-propanamide in several conformations and under different conditions resulting in 6 different crystal structures, X-ray diffraction structure determination and analysis at resolutions of 1.93-2.85 A, respectively, overview
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
construction of a short and a long CBS domain deletion mutant variant, BaIMPDHDELTAS and BaIMPDHDELTAL. Deletion of residues Val95-Thr200 and Glu92-Arg220, respectively
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimethyl sulfoxide
Q81W29
up to 15-20% increase IMP dehydrogenase activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant soluble His-tagged enzyme from Escherichia coli strain BL21(DE3)/pDIA17 by nickel affinity chromatography and gel filtration
Q81W29
Ni-NTA Sepharose bead chromatography and Superdex 200 gel filtration
recombinant His-tagged long and short enzyme CBS-deletion mutants, BaIMPDHDELTAL and BaIMPDHDELTAS, from Escherichia coli by nickel affinity chromatography , tag cleavage by TEV protease, and removal by another step of nickel affinity chromatography, followed by dialysis
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene guaB, sequence comparisons, functional recombinant overexpression of the soluble His-tagged enzyme in Escherichia coli strain BL21(DE3)/pDIA17
Q81W29
expressed in Escherichia coli BL21 cells
gene impdh, sequence comparisons, recombinant expression of N-terminally His-tagged long and short enzyme CBS-deletion mutants, BaIMPDHDELTAL and BaIMPDHDELTAS, in Escherichia coli
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
MPDH inhibitors are used as immunosuppressive, antiviral, and anticancer agents
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Makowska-Grzyska, M.; Kim, Y.; Wu, R.; Wilton, R.; Gollapalli, D.R.; Wang, X.K.; Zhang, R.; Jedrzejczak, R.; Mack, J.C.; Maltseva, N.; Mulligan, R.; Binkowski, T.A.; Gornicki, P.; Kuhn, M.L.; Anderson, W.F.; Hedstrom, L.; Joachimiak, A.
Bacillus anthracis inosine 5-monophosphate dehydrogenase in action: the first bacterial series of structures of phosphate ion-, substrate-, and product-bound complexes
Biochemistry
51
6148-6163
2012
Campylobacter jejuni, Bacillus anthracis (Q81W29), Bacillus anthracis
Manually annotated by BRENDA team
Makowska-Grzyska, M.; Kim, Y.; Maltseva, N.; Osipiuk, J.; Gu, M.; Zhang, M.; Mandapati, K.; Gollapalli, D.R.; Gorla, S.K.; Hedstrom, L.; Joachimiak, A.
A novel cofactor-binding mode in bacterial IMP dehydrogenases explains inhibitor selectivity
J. Biol. Chem.
290
5893-5911
2015
Bacillus anthracis, Campylobacter jejuni, Clostridium perfringens, Vibrio cholerae serotype O1
Manually annotated by BRENDA team
Alexandre, T.; Raynal, B.; Rayna, B.; Munier-Lehmann, H.
Two classes of bacterial IMPDHs according to their quaternary structures and catalytic properties
PLoS ONE
10
e0116578
2015
Acinetobacter baumannii, Bacillus thuringiensis, Klebsiella pneumoniae, Neisseria meningitidis (A1KU15), Staphylococcus aureus (P99106), Burkholderia thailandensis (Q2SWW9), Legionella pneumophila subsp. pneumophila (Q5ZUR9), Bacillus anthracis (Q81W29), Staphylococcus aureus N315 (P99106), Bacillus thuringiensis BGSC 4AJ1, Legionella pneumophila subsp. pneumophila Philadelphia 1 (Q5ZUR9), Acinetobacter baumannii 5377, Klebsiella pneumoniae 52145
Manually annotated by BRENDA team
Yu, R.; Kim, Y.; Maltseva, N.; Braunstein, P.; Joachimiak, A.; Hedstrom, L.
Oxanosine monophosphate is a covalent inhibitor of inosine 5'-monophosphate dehydrogenase
Chem. Res. Toxicol.
32
456-466
2019
Cryptosporidium parvum, Tritrichomonas foetus, Campylobacter jejuni (A0A2R4D3F6), Bacillus anthracis (A0A6L8P2U9), Homo sapiens (P12268)
Manually annotated by BRENDA team
Juvale, K.; Shaik, A.; Kirubakaran, S.
Inhibitors of inosine 5'-monophosphate dehydrogenase as emerging new generation antimicrobial agents
MedChemComm
10
1290-1301
2019
Bacillus anthracis, Bacillus anthracis (A0A6L8P2U9), Cryptosporidium parvum, Clostridium perfringens (A0A127ELD1), Campylobacter jejuni (A0A2R4D3F6), Mycolicibacterium thermoresistibile (G7CNL4), Mycobacterium tuberculosis (P9WKI7), Listeria monocytogenes (Q926Y9), Pseudomonas aeruginosa (Q9HXM5), Vibrio cholerae (Q9KTW3), Bacillus anthracis Ames, Mycolicibacterium thermoresistibile ATCC 19527 (G7CNL4), Listeria monocytogenes ATCC BAA-679 (Q926Y9), Mycobacterium tuberculosis H37Rv (P9WKI7), Vibrio cholerae ATCC 39315 (Q9KTW3)
Manually annotated by BRENDA team