GUAB1_MYCS2
ID GUAB1_MYCS2 Reviewed; 478 AA.
AC A0QYE8; I7GA39;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 108.
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 {ECO:0000303|PubMed:35338694};
GN OrderedLocusNames=MSMEG_3634 {ECO:0000312|EMBL:ABK74721.1},
GN MSMEI_3548 {ECO:0000312|EMBL:AFP40011.1};
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP GMP, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
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). Is not essential for viability, but may contribute
CC to the regulation of the purine nucleotide pool by recycling GMP to IMP
CC (PubMed:35338694). {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 -!- ACTIVITY REGULATION: Activity is allosterically regulated by the
CC ATP/GTP ratio in a pH-dependent manner (PubMed:35338694). At pH 7.8,
CC GTP has only a minor positive effect and ATP only a minor negative
CC effect on the activity, however, at lower pH values, the effects of ATP
CC and GTP increase (PubMed:35338694). ATP-dependent inhibition can be
CC restored by increasing GTP concentration (PubMed:35338694). IMP and XMP
CC are competitive inhibitors (PubMed:35338694).
CC {ECO:0000269|PubMed:35338694}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for NADPH (at pH 7.8) {ECO:0000269|PubMed:35338694};
CC KM=63 uM for NADPH (at pH 6.6) {ECO:0000269|PubMed:35338694};
CC pH dependence:
CC Optimum pH is 7.4-7.8. {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 (PubMed:35338694). The
CC oligomerization state is regulated by ligands and pH (PubMed:35338694).
CC {ECO:0000269|PubMed:35338694}.
CC -!- DISRUPTION PHENOTYPE: Knocked out mutant does not require any purine
CC supplement for the growth and does not exhibit any growth defects in
CC media containing hypoxanthine, guanine and adenine.
CC {ECO:0000269|PubMed:35338694}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. GuaB1 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_02250, ECO:0000305}.
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; CP000480; ABK74721.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP40011.1; -; Genomic_DNA.
DR RefSeq; WP_011729218.1; NZ_SIJM01000008.1.
DR RefSeq; YP_887936.1; NC_008596.1.
DR PDB; 7OY9; X-ray; 2.80 A; A/B/C/D/E/F/G/H=2-478.
DR PDB; 7R50; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=2-478.
DR PDBsum; 7OY9; -.
DR PDBsum; 7R50; -.
DR STRING; 246196.MSMEI_3548; -.
DR EnsemblBacteria; ABK74721; ABK74721; MSMEG_3634.
DR GeneID; 66735017; -.
DR KEGG; msm:MSMEG_3634; -.
DR PATRIC; fig|246196.19.peg.3581; -.
DR eggNOG; COG0516; Bacteria.
DR eggNOG; COG0517; Bacteria.
DR OMA; TYDDVFM; -.
DR OrthoDB; 532857at2; -.
DR UniPathway; UPA00591; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IEA:InterPro.
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 3D-structure; Allosteric enzyme; CBS domain; NADP; Oxidoreductase;
KW Purine salvage; Reference proteome; Repeat.
FT CHAIN 1..478
FT /note="GMP reductase"
FT /id="PRO_0000456250"
FT DOMAIN 95..152
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 153..211
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT ACT_SITE 302
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 245..247
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 295..297
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P50097"
SQ SEQUENCE 478 AA; 49593 MW; 3DEF44FB65A19B0B CRC64;
MRFLDGHTPA YDLTYNDVFV VPGRSDVASR FDVDLSTVDG SGTTIPVVVA NMTAVAGRRM
AETVARRGGI VVLPQDLPIT AVSETVDFVK SRDLVVDTPV TLSPEDSVSD ANALLHKRAH
GAAVVVFEGR PIGLVTEANC AGVDRFARVR DIALSDFVTA PVGTDPREVF DLLEHAPIDV
AVMTAPDGTL AGVLTRTGAI RAGIYTPAVD AKGRLRIAAA VGINGDVGAK AQALAEAGAD
LLVIDTAHGH QAKMLDAIKA VASLDLGLPL VAGNVVSAEG TRDLIEAGAS IVKVGVGPGA
MCTTRMMTGV GRPQFSAVVE CAAAARQLGG HVWADGGVRH PRDVALALAA GASNVMIGSW
FAGTYESPGD LLFDRDDRPY KESYGMASKR AVAARTAGDS SFDRARKGLF EEGISTSRMS
LDPARGGVED LLDHITSGVR STCTYVGAAN LPELHEKVVL GVQSAAGFAE GHPLPAGW
