IMPDHIMP dehydrogenase / GMP reductase domain |
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SMART accession number: | SM01240 |
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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. |
Family alignment: |
There are 30692 IMPDH domains in 30689 proteins in SMART's nrdb database.
Click on the following links for more information.
- Evolution (species in which this domain is found)
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Taxonomic distribution of proteins containing IMPDH domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with IMPDH domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing IMPDH domain in the selected taxonomic class.
- Cellular role (predicted cellular role)
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Cellular role: metabolism
- Literature (relevant references for this domain)
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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
- Display abstract
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
- Display abstract
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 Main view 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)
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PFAM IMPDH