IMDH_TRYBB
ID IMDH_TRYBB Reviewed; 512 AA.
AC P50098;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMP dehydrogenase {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMPD {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMPDH {ECO:0000255|HAMAP-Rule:MF_03156};
DE EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_03156};
OS Trypanosoma brucei brucei.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=5702;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Eatro 164 / ISTat 1.7;
RX PubMed=7961861; DOI=10.1016/s0021-9258(19)62002-8;
RA Wilson K., Berens R.L., Sifri C.D., Ullman B.;
RT "Amplification of the inosinate dehydrogenase gene in Trypanosoma brucei
RT gambiense due to an increase in chromosome copy number.";
RL J. Biol. Chem. 269:28979-28987(1994).
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_03156}.
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_03156};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03156};
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_03156}.
CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC from IMP: step 1/1. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SUBCELLULAR LOCATION: Glycosome {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_03156}.
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; M97794; AAB46420.1; -; Genomic_DNA.
DR PIR; A55407; A55407.
DR PDB; 6RFU; X-ray; 2.80 A; A/B=1-512.
DR PDBsum; 6RFU; -.
DR AlphaFoldDB; P50098; -.
DR SASBDB; P50098; -.
DR SMR; P50098; -.
DR BRENDA; 1.1.1.205; 6519.
DR UniPathway; UPA00601; UER00295.
DR GO; GO:0020015; C:glycosome; IEA:UniProtKB-SubCell.
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; 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 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; Glycosome; GMP biosynthesis; Metal-binding; NAD;
KW Oxidoreductase; Peroxisome; Potassium; Purine biosynthesis; Repeat.
FT CHAIN 1..512
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000093677"
FT DOMAIN 110..169
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT DOMAIN 173..231
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT MOTIF 510..512
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 325
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 423
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 268..270
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 318..320
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 320
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_03156"
FT BINDING 322
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_03156"
FT BINDING 323
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 325
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_03156"
FT BINDING 358..360
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 381..382
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 405..409
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 435
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 494
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_03156"
FT BINDING 495
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_03156"
FT HELIX 4..7
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 49..54
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:6RFU"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 72..81
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 93..104
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 123..132
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 156..159
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 188..198
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 210..217
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 218..226
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 250..260
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 275..287
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 292..298
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 301..310
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 315..317
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 337..349
FT /evidence="ECO:0007829|PDB:6RFU"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 364..372
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 376..381
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 394..397
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 400..403
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 447..465
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 470..478
FT /evidence="ECO:0007829|PDB:6RFU"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:6RFU"
FT HELIX 489..492
FT /evidence="ECO:0007829|PDB:6RFU"
SQ SEQUENCE 512 AA; 55709 MW; 1A86C46AE6445045 CRC64;
MENTNLRTKT LRDGTTAEEL FSQDGLSFND FIILPGFIDF DSSKVNVSGQ FTKNILLHLP
LVSSPMDTVT ESSMARAMAL MGGIGVIHNN CTVEQQARMV RSVKLYRNGF IMKPKSVSPD
VPVSTIRNIK SEKGISGILV TEGGKYDGKL LGIVCTKDID FVKDASAPVS QYMTRRENMT
VERYPIKLEE AMDVLNRSRH GYLPVLNDKD EVVCLCSRRD AVRARDYPNS SLDRNGHLLC
AAATSTREAD KGRVAALSEA GIDVLVLDSS QGNTIYQVSF IRWVKKTYPH LEVVAGNVVT
QDQAKNLIDA GADSLRIGMG SGSICITQEV LACGRPQATA IYKVARYAAS RGVPCVADGG
LRNVGDVCKA LAVGANVAML GSMIAGTSET PGEYFFKDGM RLKGYRGMGS IDAMLQGRES
GKRYLSENET LQVAQGVAGA VLDKGSVLKL LAYIHKGLQQ SAQDIGEVSF DAIREKVYEG
QVLFNRRTLT AQSEGAVHSL HHYERKLFAS KL
