The domain within your query sequence starts at position 28 and ends at position 248; the E-value for the IMPDH domain shown below is 1.3e-18.

DGLTYNDFLILPGYIDFTADQVDLTSALTKKITLKTPLVSSPMDTVTEAGMAIAMAKYEQ
GFITDPVVLSPKDRVRDVFEAKARHGFCGIPITDTGRMGSRLVGIISSRDIDFLKEEEHD
RFLEEIMTKREDLVVAPAGVTLKEANEILQRSKKGKLPIVNENDELVAIIARTDLKKNRD
YPLASKDAKKQLLCGAAIGTHEDDKYRLDLLALAGVDVVVL

IMPDH

IMP dehydrogenase / GMP reductase domain

• SMART accession number: SM01240
• Description: This family is involved in biosynthesis of guanosine nucleotide. Members of this family contain a TIM barrel structure. In the inosine monophosphate dehydrogenases 2 CBS domains are inserted in the TIM barrel (PMID: 10200156). This family is a member of the common phosphate binding site TIM barrel family.

There are 30692 IMPDH domains in 30689 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: metabolism

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Zhang R et al.
• Characteristics and crystal structure of bacterial inosine-5'-monophosphatedehydrogenase.
• Biochemistry. 1999; 38: 4691-700

IMP dehydrogenase (IMPDH) is an essential enzyme that catalyzes the first stepunique to GTP synthesis. To provide a basis for the evaluation of IMPDHinhibitors as antimicrobial agents, we have expressed and characterized IMPDHfrom the pathogenic bacterium Streptococcus pyogenes. Our results show that thebiochemical and kinetic characteristics of S. pyogenes IMPDH are similar to otherbacterial IMPDH enzymes. However, the lack of sensitivity to mycophenolic acidand the Km for NAD (1180 microM) exemplify some of the differences between thebacterial and mammalian IMPDH enzymes, making it an attractive target forantimicrobial agents. To evaluate the basis for these differences, we determined the crystal structure of the bacterial enzyme at 1.9 A with substrate bound inthe catalytic site. The structure was determined usingselenomethionine-substituted protein and multiwavelength anomalous (MAD) analysisof data obtained with synchrotron radiation from the undulator beamline (19ID) ofthe Structural Biology Center at Argonne's Advanced Photon Source. S. pyogenesIMPDH is a tetramer with its four subunits related by a crystallographic 4-foldaxis. The protein is composed of two domains: a TIM barrel domain that embodiesthe catalytic framework and a cystathione beta-synthase (CBS) dimer domain of so far unknown function. Using information provided by sequence alignments and thecrystal structure, we prepared several site-specific mutants to examine the role of various active site regions in catalysis. These variants implicate the active site flap as an essential catalytic element and indicate there are significantdifferences in the catalytic environment of bacterial and mammalian IMPDHenzymes. Comparison of the structure of bacterial IMPDH with the known partialstructures from eukaryotic organisms will provide an explanation of theirdistinct properties and contribute to the design of specific bacterial IMPDHinhibitors.

• Whitby FG et al.
• Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenaseand the enzyme-product complex.
• Biochemistry. 1997; 36: 10666-74

Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target forthe control of parasitic infections. The enzyme catalyzes the oxidation ofinosine monophosphate (IMP) to xanthosine monophosphate (XMP), the committed stepin de novo guanosine monophosphate (GMP) biosynthesis. We have determined thecrystal structures of IMPDH from the protozoan parasite Tritrichomonas foetus in the apo form at 2.3 A resolution and the enzyme-XMP complex at 2.6 A resolution. Each monomer of this tetrameric enzyme is comprised of two domains, the largestof which includes an eight-stranded parallel beta/alpha-barrel that contains the enzyme active site at the C termini of the barrel beta-strands. A second domain, comprised of residues 102-220, is disordered in the crystal. IMPDH is expected tobe active as a tetramer, since the active site cavity is formed by strands fromadjacent subunits. An intrasubunit disulfide bond, seen in the crystal structure,may stabilize the protein in a less active form, as high concentrations ofreducing agent have been shown to increase enzyme activity. Disorder at theactive site suggests that a high degree of flexibility may be inherent in thecatalytic function of IMPDH. Unlike IMPDH from other species, the T. foetusenzyme has a single arginine that is largely responsible for coordinating thesubstrate phosphate in the active site. This structural uniqueness may facilitatestructure-based identification and design of compounds that specifically inhibit the parasite enzyme.

Structure (3D structures containing this domain)

3D Structures of IMPDH domains in PDB

PDB code	Title
1ak5	INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH) FROM TRITRICHOMONAS FOETUS
1b3o	TERNARY COMPLEX OF HUMAN TYPE-II INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP AND SELENAZOLE ADENINE DINUCLEOTIDE
1eep	2.4 A RESOLUTION CRYSTAL STRUCTURE OF BORRELIA BURGDORFERI INOSINE 5'-MONPHOSPHATE DEHYDROGENASE IN COMPLEX WITH A SULFATE ION
1jcn	BINARY COMPLEX OF HUMAN TYPE-I INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP
1jr1	Crystal structure of Inosine Monophosphate Dehydrogenase in complex with Mycophenolic Acid
1lrt	CRYSTAL STRUCTURE OF TERNARY COMPLEX OF TRITRICHOMONAS FOETUS INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE: STRUCTURAL CHARACTERIZATION OF NAD+ SITE IN MICROBIAL ENZYME
1me7	Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with RVP and MOA bound
1me8	Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with RVP bound
1me9	Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP bound
1meh	Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP and MOA bound
1mei	Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with XMP and mycophenolic acid bound
1mew	Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with XMP and NAD bound
1nf7	Ternary complex of the human type II Inosine Monophosphate Dedhydrogenase with Ribavirin Monophosphate and C2-Mycophenolic Adenine Dinucleotide
1nfb	Ternary complex of the human type II Inosine Monophosphate Dedhydrogenase with 6Cl-IMP and NAD
1pvn	The crystal structure of the complex between IMP dehydrogenase catalytic domain and a transition state analogue MZP
1vrd	Crystal structure of Inosine-5'-monophosphate dehydrogenase (TM1347) from THERMOTOGA MARITIMA at 2.18 A resolution
1ypf	Crystal Structure of GuaC (BA5705) from Bacillus anthracis at 1.8 A Resolution
1zfj	INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH; EC 1.1.1.205) FROM STREPTOCOCCUS PYOGENES
2a1y	Crystal Structure of GuaC-GMP complex from Bacillus anthracis at 2.26 A Resolution.
2a7r	Crystal structure of human Guanosine Monophosphate reductase 2 (GMPR2)
2ble	Structure of human guanosine monophosphate reductase GMPR1 in complex with GMP
2bwg	Structure of human guanosine monophosphate reductase GMPR1 in complex with GMP
2bzn	Crystal structure of human guanosine monophosphate reductase 2 GMPR2 in complex with IMP
2c6q	Crystal structure of human guanosine monophosphate reductase 2 GMPR2 in complex with IMP and NADPH
2cu0	Crystal structure of inosine-5'-monophosphate dehydrogenase from Pyrococcus horikoshii OT3
2qr6	Crystal structure of IMP dehydrogenase/GMP reductase-like protein (NP_599840.1) from Corynebacterium glutamicum ATCC 13032 Kitasato at 1.50 A resolution
3ffs	The Crystal Structure of Cryptosporidium parvum Inosine-5'-Monophosphate Dehydrogenase
3khj	C. parvum inosine monophosphate dehydrogenase bound by inhibitor C64
3r2g	Crystal structure of Inosine 5' monophosphate dehydrogenase from Legionella pneumophila
3tsb	Crystal Structure of Inosine-5'-monophosphate Dehydrogenase from Bacillus anthracis str. Ames
3tsd	Crystal Structure of Inosine-5'-monophosphate Dehydrogenase from Bacillus anthracis str. Ames complexed with XMP
3usb	Crystal Structure of Bacillus anthracis Inosine Monophosphate Dehydrogenase in the complex with IMP
3zfh	Crystal structure of Pseudomonas aeruginosa inosine 5'-monophosphate dehydrogenase
4af0	Crystal structure of cryptococcal inosine monophosphate dehydrogenase
4avf	Crystal structure of Pseudomonas aeruginosa inosine 5'-monophosphate dehydrogenase
4dqw	Crystal Structure Analysis of PA3770
4fez	Inosine 5'-monophosphate dehydrogenase from Vibrio cholerae, deletion mutant
4fo4	Inosine 5'-monophosphate dehydrogenase from Vibrio cholerae, deletion mutant, complexed with IMP and mycophenolic acid
4fxs	Inosine 5'-monophosphate dehydrogenase from Vibrio cholerae complexed with IMP and mycophenolic acid
4ix2	Inosine 5'-monophosphate dehydrogenase from Vibrio cholerae, deletion mutant, complexed with IMP
4ixh	Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Cryptosporidium parvum
4mjm	Crystal Structure of the Inosine 5'-monophosphate Dehydrogenase, with a Short Internal Deletion of CBS Domain from Bacillus anthracis str. Ames
4my1	Crystal Structure of the Inosine 5'-monophosphate Dehydrogenase, with a Internal Deletion of CBS Domain from Bacillus anthracis str. Ames complexed with P68
4my8	Crystal Structure of the Inosine 5'-monophosphate Dehydrogenase with an Internal Deletion of the CBS Domain from Bacillus anthracis str. Ames complexed with inhibitor Q21
4my9	4MY9
4mya	Crystal Structure of the Inosine 5'-monophosphate Dehydrogenase with an Internal Deletion of the CBS Domain from Bacillus anthracis str. Ames complexed with inhibitor A110
4myx	4MYX
4mz1	Crystal Structure of the Inosine 5'-monophosphate Dehydrogenase, with a Internal Deletion of CBS Domain from Campylobacter jejuni complexed with inhibitor compound P12
4mz8	4MZ8
4q32	4Q32
4q33	4Q33
4qj1	4QJ1
4qm1	4QM1
4qne	4QNE
4qq3	4QQ3
4r7j	4R7J
4rv8	4RV8
4x3z	4X3Z
4xtd	4XTD
4xti	4XTI
4xwu	4XWU
4z0g	4Z0G
4z87	4Z87
4zqm	4ZQM
4zqn	4ZQN
4zqo	4ZQO
4zqp	4ZQP
4zqr	4ZQR
5ahl	5AHL
5ahm	5AHM
5ahn	5AHN
5j5r	5J5R
5k4x	5K4X
5k4z	5K4Z

Links (links to other resources describing this domain)

• PFAM: IMPDH