GUAB1_MYCTU
ID GUAB1_MYCTU Reviewed; 479 AA.
AC P9WKI3; L0TAS0; P65172; Q50591;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=GMP reductase {ECO:0000305};
DE EC=1.7.1.7 {ECO:0000269|PubMed:35338694};
DE AltName: Full=Guanosine 5'-monophosphate reductase {ECO:0000303|PubMed:35338694};
DE Short=GMPR {ECO:0000303|PubMed:35338694};
GN Name=guaB1; OrderedLocusNames=Rv1843c; ORFNames=MTCY1A11.01, MTCY359.30;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP LACK OF IMP DEHYDROGENASE ACTIVITY, AND FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21081761; DOI=10.1099/mic.0.042549-0;
RA Usha V., Gurcha S.S., Lovering A.L., Lloyd A.J., Papaemmanouil A.,
RA Reynolds R.C., Besra G.S.;
RT "Identification of novel diphenyl urea inhibitors of Mt-GuaB2 active
RT against Mycobacterium tuberculosis.";
RL Microbiology 157:290-299(2011).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=35338694; DOI=10.1111/febs.16448;
RA Knejzlik Z., Dolezal M., Herkommerova K., Clarova K., Klima M., Dedola M.,
RA Zbornikova E., Rejman D., Pichova I.;
RT "The mycobacterial guaB1 gene encodes a guanosine 5'-monophosphate
RT reductase with a cystathionine-beta-synthase domain.";
RL FEBS J. 0:0-0(2022).
CC -!- FUNCTION: Involved in the purine-salvage pathway (PubMed:35338694).
CC Catalyzes the NADPH-dependent conversion of GMP to IMP
CC (PubMed:35338694). Has no inosine-5'-monophosphate dehydrogenase
CC (IMPDH) activity (PubMed:21081761). {ECO:0000269|PubMed:21081761,
CC ECO:0000269|PubMed:35338694}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=IMP + NADP(+) + NH4(+) = GMP + 2 H(+) + NADPH;
CC Xref=Rhea:RHEA:17185, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58053, ChEBI:CHEBI:58115,
CC ChEBI:CHEBI:58349; EC=1.7.1.7; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_02250, ECO:0000269|PubMed:35338694};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17187;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02250,
CC ECO:0000269|PubMed:35338694};
CC -!- COFACTOR:
CC Name=a monovalent cation; Xref=ChEBI:CHEBI:60242;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02250,
CC ECO:0000269|PubMed:35338694};
CC Note=Activity is highest with Rb(+), followed by K(+), NH4(+) and
CC Cs(+). {ECO:0000269|PubMed:35338694};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=63 uM for NADPH (at pH 7.8) {ECO:0000269|PubMed:35338694};
CC pH dependence:
CC Optimum pH is 7.6-8.2. {ECO:0000269|PubMed:35338694};
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway.
CC {ECO:0000255|HAMAP-Rule:MF_02250, ECO:0000305|PubMed:35338694}.
CC -!- SUBUNIT: Homooctamer composed of two tetramers.
CC {ECO:0000250|UniProtKB:A0QYE8}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. GuaB1 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_02250, ECO:0000305}.
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DR EMBL; AL123456; CCP44609.1; -; Genomic_DNA.
DR PIR; C70664; C70664.
DR RefSeq; NP_216359.1; NC_000962.3.
DR RefSeq; WP_003902189.1; NC_018143.2.
DR AlphaFoldDB; P9WKI3; -.
DR SMR; P9WKI3; -.
DR STRING; 83332.Rv1843c; -.
DR PaxDb; P9WKI3; -.
DR DNASU; 885714; -.
DR GeneID; 885714; -.
DR KEGG; mtu:Rv1843c; -.
DR PATRIC; fig|83332.111.peg.2049; -.
DR TubercuList; Rv1843c; -.
DR eggNOG; COG0516; Bacteria.
DR eggNOG; COG0517; Bacteria.
DR OMA; TYDDVFM; -.
DR PhylomeDB; P9WKI3; -.
DR UniPathway; UPA00591; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IEA:InterPro.
DR CDD; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_02250; GMPR_GuaB1; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR005990; IMP_DH.
DR InterPro; IPR005991; IMP_DH-rel1.
DR InterPro; IPR001093; IMP_DH_GMPRt.
DR Pfam; PF00571; CBS; 1.
DR Pfam; PF00478; IMPDH; 1.
DR PIRSF; PIRSF000130; IMPDH; 1.
DR SUPFAM; SSF54631; SSF54631; 1.
DR TIGRFAMs; TIGR01303; IMP_DH_rel_1; 1.
DR PROSITE; PS51371; CBS; 2.
PE 1: Evidence at protein level;
KW CBS domain; NADP; Oxidoreductase; Purine salvage; Reference proteome;
KW Repeat.
FT CHAIN 1..479
FT /note="GMP reductase"
FT /id="PRO_0000093785"
FT DOMAIN 96..153
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 154..212
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT ACT_SITE 303
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 246..248
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 296..298
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P50097"
SQ SEQUENCE 479 AA; 49965 MW; F34DAB1E6806B463 CRC64;
MMRFLDGHPP GYDLTYNDVF IVPNRSEVAS RFDVDLSTAD GSGTTIPVVV ANMTAVAGRR
MAETVARRGG IVILPQDLPI PAVKQTVAFV KSRDLVLDTP VTLAPDDSVS DAMALIHKRA
HGVAVVILEG RPIGLVRESS CLGVDRFTRV RDIAVTDYVT APAGTEPRKI FDLLEHAPVD
VAVLTDADGT LAGVLSRTGA IRAGIYTPAT DSAGRLRIGA AVGINGDVGA KARALAEAGV
DVLVIDTAHG HQVKTLDAIK AVSALDLGLP LAAGNVVSAE GTRDLLKAGA NVVKVGVGPG
AMCTTRMMTG VGRPQFSAVL ECASAARQLG GHIWADGGIR HPRDVALALA AGASNVMIGS
WFAGTYESPG DLMRDRDDQP YKESYGMASK RAVVARTGAD NPFDRARKAL FEEGISTSRM
GLDPDRGGVE DLIDHITSGV RSTCTYVGAS NLAELHERAV VGVQSGAGFA EGHPLPAGW
