ID IMDH_STRP3 Reviewed; 493 AA. AC P0DB88; Q8K5G1; DT 27-JUL-2011, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 1. DT 27-MAR-2024, entry version 63. 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}; Synonyms=impD; GN OrderedLocusNames=SpyM3_1857; OS Streptococcus pyogenes serotype M3 (strain ATCC BAA-595 / MGAS315). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Streptococcus. OX NCBI_TaxID=198466; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-595 / MGAS315; RX PubMed=12122206; DOI=10.1073/pnas.152298499; RA Beres S.B., Sylva G.L., Barbian K.D., Lei B., Hoff J.S., Mammarella N.D., RA Liu M.-Y., Smoot J.C., Porcella S.F., Parkins L.D., Campbell D.S., RA Smith T.M., McCormick J.K., Leung D.Y.M., Schlievert P.M., Musser J.M.; RT "Genome sequence of a serotype M3 strain of group A Streptococcus: phage- RT encoded toxins, the high-virulence phenotype, and clone emergence."; RL Proc. Natl. Acad. Sci. U.S.A. 99:10078-10083(2002). 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; AE014074; AAM80464.1; -; Genomic_DNA. DR RefSeq; WP_011055116.1; NC_004070.1. DR AlphaFoldDB; P0DB88; -. DR SMR; P0DB88; -. DR KEGG; spg:SpyM3_1857; -. DR HOGENOM; CLU_022552_1_0_9; -. DR UniPathway; UPA00601; UER00295. DR Proteomes; UP000000564; 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 3: Inferred from homology; KW CBS domain; GMP biosynthesis; Metal-binding; NAD; Oxidoreductase; KW Potassium; Purine biosynthesis; Repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250" FT CHAIN 2..493 FT /note="Inosine-5'-monophosphate dehydrogenase" FT /id="PRO_0000093716" FT DOMAIN 97..155 FT /note="CBS 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT DOMAIN 159..219 FT /note="CBS 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT ACT_SITE 310 FT /note="Thioimidate intermediate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT ACT_SITE 406 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 253 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 303..305 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 305 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 307 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 308 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 310 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 343..345 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 366..367 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 390..394 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 421 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964" FT BINDING 475 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 476 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 477 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" SQ SEQUENCE 493 AA; 52806 MW; 429190D9B2A57B09 CRC64; MSNWDTKFLK KGYTFDDVLL IPAESHVLPN EVDLKTKLAD NLTLNIPIIT AAMDTVTGSK MAIAIARAGG LGVIHKNMSI TEQAEEVRKV KRSENGVIID PFFLTPEHKV SEAEELMQRY RISGVPIVET LANRKLVGII TNRDMRFISN YNAPISEHMT SEHLVTAAVG TDLETAERIL HEHRIEKLPL VDNSGRLSGL ITIKDIEKVI EFPHAAKDEF GRLLVAAAVG VTSDTFERAE ALFEAGADAI VIDTAHGHSA GVLRKIAEIR AHFPNRTLIA GNIATAEGAR ALYDAGVDVV KVGIGPGSIC TTRVVAGVGV PQVTAIYDAA AVAREYGKTI IADGGIKYSG DIVKALAAGG NAVMLGSMFA GTDEAPGETE IYQGRKFKTY RGMGSIAAMK KGSSDRYFQG SVNEANKLVP EGIEGRVAYK GAASDIVFQM LGGIRSGMGY VGAGDIQELH ENAQFVEMSG AGLIESHPHD VQITNEAPNY SVH //