ID IMDH_STRPY Reviewed; 493 AA. AC P0C0H6; P50099; P68838; DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 24-JAN-2024, entry version 100. 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; OS Streptococcus pyogenes. OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Streptococcus. OX NCBI_TaxID=1314; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7489916; DOI=10.1016/0378-1119(95)00422-3; RA Ashbaugh C.D., Wessels M.R.; RT "Cloning, sequence analysis and expression of the group A streptococcal RT guaB gene encoding inosine monophosphate dehydrogenase."; RL Gene 165:57-60(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-20, X-RAY RP CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH IMP, BIOPHYSICOCHEMICAL RP PROPERTIES, MASS SPECTROMETRY, SUBUNIT, AND MUTAGENESIS OF ARG-406; GLU-421 RP AND TYR-450. RX PubMed=10200156; DOI=10.1021/bi982858v; RA Zhang R.G., Evans G., Rotella F.J., Westbrook E.M., Beno D., Huberman E., RA Joachimiak A., Collart F.R.; RT "Characteristics and crystal structure of bacterial inosine-5'- RT monophosphate dehydrogenase."; RL Biochemistry 38:4691-4700(1999). 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 -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=62 uM for Inosine 5'-phosphate {ECO:0000269|PubMed:10200156}; CC KM=1180 uM for NAD(+) {ECO:0000269|PubMed:10200156}; CC pH dependence: CC Optimum pH is 7.8. {ECO:0000269|PubMed:10200156}; 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 ECO:0000269|PubMed:10200156}. CC -!- MASS SPECTROMETRY: Mass=52328; Method=MALDI; CC Evidence={ECO:0000269|PubMed:10200156}; 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; U26056; AAB03846.1; -; Genomic_DNA. DR PIR; JC4372; JC4372. DR RefSeq; WP_002991454.1; NZ_WXZK01000022.1. DR PDB; 1ZFJ; X-ray; 1.90 A; A=2-492. DR PDBsum; 1ZFJ; -. DR AlphaFoldDB; P0C0H6; -. DR SMR; P0C0H6; -. DR STRING; 1314.SD89_09625; -. DR BindingDB; P0C0H6; -. DR DrugBank; DB04566; Inosinic Acid. DR DrugBank; DB04862; Merimepodib. DR GeneID; 69901624; -. DR eggNOG; COG0516; Bacteria. DR eggNOG; COG0517; Bacteria. DR OMA; MGYCGAK; -. DR BRENDA; 1.1.1.205; 5935. DR SABIO-RK; P0C0H6; -. DR UniPathway; UPA00601; UER00295. DR EvolutionaryTrace; P0C0H6; -. 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; Direct protein sequencing; GMP biosynthesis; KW Metal-binding; NAD; Oxidoreductase; Potassium; Purine biosynthesis; Repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:10200156" FT CHAIN 2..493 FT /note="Inosine-5'-monophosphate dehydrogenase" FT /id="PRO_0000093714" 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 ECO:0000269|PubMed:10200156" 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 BINDING 366..367 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT BINDING 390..394 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" 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" FT MUTAGEN 406 FT /note="R->A: No activity." FT /evidence="ECO:0000269|PubMed:10200156" FT MUTAGEN 421 FT /note="E->Q: No activity." FT /evidence="ECO:0000269|PubMed:10200156" FT MUTAGEN 450 FT /note="Y->A: No effect." FT /evidence="ECO:0000269|PubMed:10200156" FT MUTAGEN 450 FT /note="Y->D: Reduces activity by 75%." FT /evidence="ECO:0000269|PubMed:10200156" FT CONFLICT 419 FT /note="V -> L (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT HELIX 3..6 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 15..17 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 18..20 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 29..31 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 42..50 FT /evidence="ECO:0007829|PDB:1ZFJ" FT TURN 54..56 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 59..67 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 71..74 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 80..93 FT /evidence="ECO:0007829|PDB:1ZFJ" FT TURN 94..97 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 98..100 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 106..109 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 110..119 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 123..129 FT /evidence="ECO:0007829|PDB:1ZFJ" FT TURN 131..133 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 135..141 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 142..147 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 151..154 FT /evidence="ECO:0007829|PDB:1ZFJ" FT TURN 155..157 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 173..182 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 186..191 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 195..202 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 203..211 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 226..229 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 235..245 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 248..252 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 260..272 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 274..276 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 278..283 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 286..294 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 298..302 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 312..315 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 322..335 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 339..344 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 349..357 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 361..366 FT /evidence="ECO:0007829|PDB:1ZFJ" FT TURN 367..371 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 372..374 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 379..382 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 385..391 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 396..399 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 424..428 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 433..450 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 456..462 FT /evidence="ECO:0007829|PDB:1ZFJ" FT STRAND 465..467 FT /evidence="ECO:0007829|PDB:1ZFJ" FT HELIX 470..476 FT /evidence="ECO:0007829|PDB:1ZFJ" SQ SEQUENCE 493 AA; 52807 MW; 9C317AD598CB5740 CRC64; MSNWDTKFLK KGYTFDDVLL IPAESHVLPN EVDLKTKLAD NLTLNIPIIT AAMDTVTGSK MAIAIARAGG LGVIHKNMSI TEQAEEVRKV KRSENGVIID PFFLTPEHKV SEAEELMQRY RISGVPIVET LANRKLVGII TNRDMRFISD 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 //