ID IMDH_PYRHO Reviewed; 486 AA. AC O58045; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 27-MAR-2024, entry version 149. DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01964}; DE Short=IMP dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01964}; DE Short=IMPD {ECO:0000255|HAMAP-Rule:MF_01964}; DE Short=IMPDH {ECO:0000255|HAMAP-Rule:MF_01964}; DE EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_01964}; GN Name=guaB {ECO:0000255|HAMAP-Rule:MF_01964}; OrderedLocusNames=PH0307; OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC OS 100139 / OT-3). OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae; OC Pyrococcus. OX NCBI_TaxID=70601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3; RX PubMed=9679194; DOI=10.1093/dnares/5.2.55; RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S., RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K., RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T., RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T., RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.; RT "Complete sequence and gene organization of the genome of a hyper- RT thermophilic archaebacterium, Pyrococcus horikoshii OT3."; RL DNA Res. 5:55-76(1998). RN [2] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH XMP. RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3; RG RIKEN structural genomics initiative (RSGI); RT "Crystal structure of inosine-5'-monophosphate dehydrogenase from RT Pyrococcus horikoshii OT3."; RL Submitted (JUL-2011) to the PDB data bank. CC -!- FUNCTION: Catalyzes the conversion of inosine 5'-phosphate (IMP) to CC xanthosine 5'-phosphate (XMP), the first committed and rate-limiting CC step in the de novo synthesis of guanine nucleotides, and therefore CC plays an important role in the regulation of cell growth. CC {ECO:0000255|HAMAP-Rule:MF_01964}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + IMP + NAD(+) = H(+) + NADH + XMP; Xref=Rhea:RHEA:11708, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57464, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58053; CC EC=1.1.1.205; Evidence={ECO:0000255|HAMAP-Rule:MF_01964}; CC -!- COFACTOR: CC Name=K(+); Xref=ChEBI:CHEBI:29103; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01964}; CC -!- ACTIVITY REGULATION: Mycophenolic acid (MPA) is a non-competitive CC inhibitor that prevents formation of the closed enzyme conformation by CC binding to the same site as the amobile flap. In contrast, mizoribine CC monophosphate (MZP) is a competitive inhibitor that induces the closed CC conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor CC inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of CC bacterial IMPDH. {ECO:0000255|HAMAP-Rule:MF_01964}. CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP CC from IMP: step 1/1. {ECO:0000255|HAMAP-Rule:MF_01964}. CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01964}. CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP- CC Rule:MF_01964}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BA000001; BAA29380.1; -; Genomic_DNA. DR PIR; E71456; E71456. DR RefSeq; WP_010884401.1; NC_000961.1. DR PDB; 2CU0; X-ray; 2.10 A; A/B=1-486. DR PDBsum; 2CU0; -. DR AlphaFoldDB; O58045; -. DR SMR; O58045; -. DR STRING; 70601.gene:9377224; -. DR EnsemblBacteria; BAA29380; BAA29380; BAA29380. DR GeneID; 1444188; -. DR KEGG; pho:PH0307; -. DR eggNOG; arCOG00612; Archaea. DR OrthoDB; 21361at2157; -. DR UniPathway; UPA00601; UER00295. DR EvolutionaryTrace; O58045; -. DR Proteomes; UP000000752; Chromosome. DR GO; GO:0003938; F:IMP dehydrogenase activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule. DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd04601; CBS_pair_IMPDH; 1. DR CDD; cd00381; IMPDH; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR HAMAP; MF_01964; IMPDH; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR000644; CBS_dom. DR InterPro; IPR046342; CBS_dom_sf. DR InterPro; IPR005990; IMP_DH. DR InterPro; IPR015875; IMP_DH/GMP_Rdtase_CS. DR InterPro; IPR001093; IMP_DH_GMPRt. DR NCBIfam; TIGR01302; IMP_dehydrog; 1. DR PANTHER; PTHR11911:SF111; INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE; 1. DR PANTHER; PTHR11911; INOSINE-5-MONOPHOSPHATE DEHYDROGENASE RELATED; 1. DR Pfam; PF00571; CBS; 2. DR Pfam; PF00478; IMPDH; 1. DR PIRSF; PIRSF000130; IMPDH; 1. DR SMART; SM00116; CBS; 2. DR SMART; SM01240; IMPDH; 1. DR SUPFAM; SSF54631; CBS-domain pair; 1. DR SUPFAM; SSF51412; Inosine monophosphate dehydrogenase (IMPDH); 1. DR PROSITE; PS51371; CBS; 2. DR PROSITE; PS00487; IMP_DH_GMP_RED; 1. PE 1: Evidence at protein level; KW 3D-structure; CBS domain; GMP biosynthesis; Metal-binding; NAD; KW Oxidoreductase; Potassium; Purine biosynthesis; Repeat. FT CHAIN 1..486 FT /note="Inosine-5'-monophosphate dehydrogenase" FT /id="PRO_0000093722" FT DOMAIN 99..154 FT /note="CBS 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT DOMAIN 156..215 FT /note="CBS 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT ACT_SITE 301 FT /note="Thioimidate intermediate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT ACT_SITE 397 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 247 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 294..296 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 296 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="ligand shared between two tetrameric FT partners" FT /note="in other chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 298 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="ligand shared between two tetrameric FT partners" FT /note="in other chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 299 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT BINDING 301 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="ligand shared between two tetrameric FT partners" FT /note="in other chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 334..336 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT BINDING 357..358 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT BINDING 381..385 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT BINDING 412 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT BINDING 466 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="ligand shared between two tetrameric FT partners" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 467 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="ligand shared between two tetrameric FT partners" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 468 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="ligand shared between two tetrameric FT partners" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT HELIX 4..9 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 17..19 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 20..22 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 38..41 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 44..52 FT /evidence="ECO:0007829|PDB:2CU0" FT TURN 56..58 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 61..69 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 73..76 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 78..80 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 82..93 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 222..225 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 230..238 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 242..247 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 254..265 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 269..276 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 279..282 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 288..293 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 303..306 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 313..326 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 330..335 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 340..348 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 352..357 FT /evidence="ECO:0007829|PDB:2CU0" FT TURN 358..362 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 370..373 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 376..382 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 387..390 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 415..419 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 424..441 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 447..453 FT /evidence="ECO:0007829|PDB:2CU0" FT STRAND 456..458 FT /evidence="ECO:0007829|PDB:2CU0" FT HELIX 461..467 FT /evidence="ECO:0007829|PDB:2CU0" SQ SEQUENCE 486 AA; 52933 MW; 6B21E9B7B3AA7C3C CRC64; MGKFVEKLEK AIKGYTFDDV LLIPQATEVE PKDVDVSTRI TPNVKLNIPI LSAAMDTVTE WEMAVAMARE GGLGVIHRNM GIEEQVEQVK RVKRAERLIV EDVITIAPDE TVDFALFLME KHGIDGLPVV EDEKVVGIIT KKDIAAREGK LVKELMTKEV ITVPESIEVE EALKIMIENR IDRLPVVDER GKLVGLITMS DLVARKKYKN AVRDENGELL VAAAVSPFDI KRAIELDKAG VDVIVVDTAH AHNLKAIKSM KEMRQKVDAD FIVGNIANPK AVDDLTFADA VKVGIGPGSI CTTRIVAGVG VPQITAVAMV ADRAQEYGLY VIADGGIRYS GDIVKAIAAG ADAVMLGNLL AGTKEAPGKE VIINGRKYKQ YRGMGSLGAM MKGGAERYYQ GGYMKTRKFV PEGVEGVVPY RGTVSEVLYQ LVGGLKAGMG YVGARNIREL KEKGEFVIIT HAGIKESHPH DIIITNEAPN YPLEKF //