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InterPro: IPR001093 IMP dehydrogenase/GMP reductase

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2802 proteins

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Accession List
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Accession

IPR001093 IMP_DH_GMPRt

Type

Family

Signatures Help

Database	ID	Name	Proteins
Pfam	PF00478	IMPDH	2802
Signatures in BioMart

InterPro Relationships Help

Parent

IPR013785 Aldolase-type TIM barrel

Children

IPR005992 IMP dehydrogenase related 2
IPR005993 Guanosine monophosphate reductase 1
IPR005994 Guanosine monophosphate reductase 2
IPR018529 IMP dehydrogenase related

Contains

IPR000644 Cystathionine beta-synthase, core
IPR015875 IMP dehydrogenase / GMP reductase, conserved site

GO Term annotation Help

Process

GO:0055114 oxidation reduction

Function

GO:0003824 catalytic activity

InterPro annotation

Entry Details in BioMart

Abstract

Synonym(s): Inosine-5'-monophosphate dehydrogenase, Inosinic acid dehydrogenase; Synonym(s): Guanosine 5'-monophosphate oxidoreductase

This entry contains two related enzymes IMP dehydrogenase and GMP reducatase. These enzymes adopt a TIM barrel structure.

IMP dehydrogenase (EC:1.1.1.205) (IMPDH) catalyzes the rate-limiting reaction of de novo GTP biosynthesis, the NAD-dependent reduction of IMP into XMP [1].

Inosine 5-phosphate + NAD⁺ + H₂O = xanthosine 5-phosphate + NADH

IMP dehydrogenase is associated with cell proliferation and is a possible target for cancer chemotherapy. Mammalian and bacterial IMPDHs are tetramers of identical chains. There are two IMP dehydrogenase isozymes in humans [2]. IMP dehydrogenase nearly always contains a long insertion that has two CBS domains within it.

GMP reductase (EC:1.7.1.7) catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP [3].

NADPH + guanosine 5-phosphate = NADP⁺ + inosine 5-phosphate + NH₃

It converts nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and maintains intracellular balance of A and G nucleotides.

Structural links Help

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SCOP: c.1.5.1 , d.37.1.1

CATH: 3.20.20.70

Database links Help

Enzyme: EC:1

PANDIT: PF00478

Blocks: IPB001093

Pfam Clan: CL0036.20

Taxonomic coverage Help

Overlapping InterPro entries Help

IPR001093

Numbers of overlapping proteins

Average numbers of overlapping amino acids

Example proteins Help

O16294 Probable GMP reductase

O42831 Putative inosine-5'-monophosphate dehydrogenase-like protein YAR075W

P12268 Inosine-5'-monophosphate dehydrogenase 2

P24547 Inosine-5'-monophosphate dehydrogenase 2

Q07152 Inosine-5'-monophosphate dehydrogenase

More proteins

Example Proteins Key

InterPro entry accession number/name and structure databases		Colour code
IPR013785	Aldolase-type TIM barrel
IPR005993	Guanosine monophosphate reductase 1
IPR000644	Cystathionine beta-synthase, core
IPR015875	IMP dehydrogenase / GMP reductase, conserved site
IPR018529	IMP dehydrogenase related
IPR001093	IMP dehydrogenase/GMP reductase
IPR005990	IMP dehydrogenase
	SWISS-MODEL
	PDB Chain
	ModBase
	SCOP Domain
	CATH Domain

Publications Open in usermanual
1.	Collart FR, Huberman E. Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs. J. Biol. Chem. 263 15769-72 1988 [PubMed: 2902093] http://intl.jbc.org/cgi/reprint/263/30/15769.pdf
2.	Natsumeda Y, Ohno S, Kawasaki H, Konno Y, Weber G, Suzuki K. Two distinct cDNAs for human IMP dehydrogenase. J. Biol. Chem. 265 5292-5 1990 [PubMed: 1969416] http://intl.jbc.org/cgi/content/abstract/265/9/5292
3.	Andrews SC, Guest JR. Nucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12. Biochem. J. 255 35-43 1988 [PubMed: 2904262] http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=EBI&pubmedid=2904262&action=stream&blobtype=pdf

Additional Reading Open in usermanual
	Zhang R, Evans G, Rotella FJ, Westbrook EM, Beno D, Huberman E, Joachimiak A, Collart FR. Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase. Biochemistry 38 1999 4691-700 [PubMed: 10200156] http://dx.doi.org/10.1021/bi982858v
	McMillan FM, Cahoon M, White A, Hedstrom L, Petsko GA, Ringe D. Crystal structure at 2.4 A resolution of Borrelia burgdorferi inosine 5'-monophosphate dehydrogenase: evidence of a substrate-induced hinged-lid motion by loop 6. Biochemistry 39 2000 4533-42 [PubMed: 10758003] http://dx.doi.org/10.1021/bi992645l
	Gan L, Petsko GA, Hedstrom L. Crystal structure of a ternary complex of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase: NAD+ orients the active site loop for catalysis. Biochemistry 41 2002 13309-17 [PubMed: 12403633] http://dx.doi.org/10.1021/bi0203785
	Whitby FG, Luecke H, Kuhn P, Somoza JR, Huete-Perez JA, Phillips JD, Hill CP, Fletterick RJ, Wang CC. Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex. Biochemistry 36 1997 10666-74 [PubMed: 9271497] http://dx.doi.org/10.1021/bi9708850
	Gan L, Seyedsayamdost MR, Shuto S, Matsuda A, Petsko GA, Hedstrom L. The immunosuppressive agent mizoribine monophosphate forms a transition state analogue complex with inosine monophosphate dehydrogenase. Biochemistry 42 2003 857-63 [PubMed: 12549902] http://dx.doi.org/10.1021/bi0271401
	Prosise GL, Luecke H. Crystal structures of Tritrichomonasfoetus inosine monophosphate dehydrogenase in complex with substrate, cofactor and analogs: a structural basis for the random-in ordered-out kinetic mechanism. J. Mol. Biol. 326 2003 517-27 [PubMed: 12559919] http://dx.doi.org/10.1016/S0022-2836(02)01383-9
	Prosise GL, Wu JZ, Luecke H. Crystal structure of Tritrichomonas foetus inosine monophosphate dehydrogenase in complex with the inhibitor ribavirin monophosphate reveals a catalysis-dependent ion-binding site. J. Biol. Chem. 277 2002 50654-9 [PubMed: 12235158] http://dx.doi.org/10.1074/jbc.M208330200

InterPro 23.1