IMDH_STRPY
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 03-AUG-2022, entry version 94.
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; Firmicutes; 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;
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 -!- 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}.
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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 BindingDB; P0C0H6; -.
DR DrugBank; DB04566; Inosinic Acid.
DR DrugBank; DB04862; Merimepodib.
DR PRIDE; P0C0H6; -.
DR GeneID; 57853535; -.
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; 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; 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
