IMDH_PYRHO
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 03-AUG-2022, entry version 144.
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;
CC Evidence={ECO:0000255|HAMAP-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}.
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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; 70601.3256697; -.
DR EnsemblBacteria; BAA29380; BAA29380; BAA29380.
DR GeneID; 1444188; -.
DR KEGG; pho:PH0307; -.
DR eggNOG; arCOG00612; Archaea.
DR OMA; MGYCGAK; -.
DR OrthoDB; 58700at2157; -.
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; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 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 PANTHER; PTHR11911; PTHR11911; 1.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00478; IMPDH; 1.
DR PIRSF; PIRSF000130; IMPDH; 1.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR TIGRFAMs; TIGR01302; IMP_dehydrog; 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
