RMLD_MYCTU
ID RMLD_MYCTU Reviewed; 304 AA.
AC P9WH09; L0TEU1; P96871; Q7D5T1;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=dTDP-4-dehydrorhamnose reductase {ECO:0000250|UniProtKB:P26392};
DE EC=1.1.1.133 {ECO:0000250|UniProtKB:P26392};
DE AltName: Full=dTDP-4-keto-L-rhamnose reductase {ECO:0000250|UniProtKB:P26392};
DE AltName: Full=dTDP-6-deoxy-L-lyxo-4-hexulose reductase {ECO:0000303|PubMed:12029057};
DE AltName: Full=dTDP-6-deoxy-L-mannose dehydrogenase {ECO:0000250|UniProtKB:P26392};
DE AltName: Full=dTDP-L-rhamnose synthase {ECO:0000250|UniProtKB:P26392};
GN Name=rmlD {ECO:0000303|PubMed:12029057}; OrderedLocusNames=Rv3266c;
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 FUNCTION IN DTDP-RHAMNOSE BIOSYNTHESIS, AND PATHWAY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12029057; DOI=10.1128/jb.184.12.3392-3395.2002;
RA Ma Y., Pan F., McNeil M.;
RT "Formation of dTDP-rhamnose is essential for growth of mycobacteria.";
RL J. Bacteriol. 184:3392-3395(2002).
RN [3]
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 [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).
CC -!- FUNCTION: Involved in the biosynthesis of the dTDP-L-rhamnose which is
CC a component of the critical linker, D-N-acetylglucosamine-L-rhamnose
CC disaccharide, which connects the galactan region of arabinogalactan to
CC peptidoglycan via a phosphodiester linkage (PubMed:12029057). Catalyzes
CC the reduction of dTDP-6-deoxy-L-lyxo-4-hexulose to yield dTDP-L-
CC rhamnose (By similarity). {ECO:0000250|UniProtKB:P26392,
CC ECO:0000269|PubMed:12029057}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dTDP-beta-L-rhamnose + NADP(+) = dTDP-4-dehydro-beta-L-
CC rhamnose + H(+) + NADPH; Xref=Rhea:RHEA:21796, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57510, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:62830; EC=1.1.1.133;
CC Evidence={ECO:0000250|UniProtKB:P26392};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P26392};
CC Note=Binds 1 Mg(2+) ion per monomer. {ECO:0000250|UniProtKB:P26392};
CC -!- PATHWAY: Carbohydrate biosynthesis; dTDP-L-rhamnose biosynthesis.
CC {ECO:0000305|PubMed:12029057}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the dTDP-4-dehydrorhamnose reductase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46085.1; -; Genomic_DNA.
DR PIR; C70978; C70978.
DR RefSeq; NP_217783.1; NC_000962.3.
DR RefSeq; WP_003899993.1; NZ_NVQJ01000003.1.
DR AlphaFoldDB; P9WH09; -.
DR SMR; P9WH09; -.
DR STRING; 83332.Rv3266c; -.
DR BindingDB; P9WH09; -.
DR ChEMBL; CHEMBL1938225; -.
DR PaxDb; P9WH09; -.
DR DNASU; 888704; -.
DR GeneID; 888704; -.
DR KEGG; mtu:Rv3266c; -.
DR TubercuList; Rv3266c; -.
DR eggNOG; COG1091; Bacteria.
DR OMA; AGETTWH; -.
DR PhylomeDB; P9WH09; -.
DR UniPathway; UPA00124; -.
DR PRO; PR:P9WH09; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0008831; F:dTDP-4-dehydrorhamnose reductase activity; IDA:MTBBASE.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019305; P:dTDP-rhamnose biosynthetic process; IDA:MTBBASE.
DR GO; GO:0045226; P:extracellular polysaccharide biosynthetic process; IGI:UniProtKB.
DR InterPro; IPR005913; dTDP_dehydrorham_reduct.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR029903; RmlD-like-bd.
DR PANTHER; PTHR10491; PTHR10491; 1.
DR Pfam; PF04321; RmlD_sub_bind; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01214; rmlD; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Magnesium; Metal-binding; NAD; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..304
FT /note="dTDP-4-dehydrorhamnose reductase"
FT /id="PRO_0000395352"
FT ACT_SITE 132
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 15..17
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 16..17
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 41..42
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 41..42
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 63..65
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 63..65
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 104..105
FT /ligand="dTDP-beta-L-rhamnose"
FT /ligand_id="ChEBI:CHEBI:57510"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 132
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 132
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 136
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 136
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT BINDING 157
FT /ligand="dTDP-beta-L-rhamnose"
FT /ligand_id="ChEBI:CHEBI:57510"
FT /evidence="ECO:0000250|UniProtKB:P26392"
FT SITE 104
FT /note="Could provide a fine-tuning to achieve optimal pKa
FT matching between active site and substrate"
FT /evidence="ECO:0000250|UniProtKB:P26392"
SQ SEQUENCE 304 AA; 32045 MW; F8D73C1674599E09 CRC64;
MAGRSERLVI TGAGGQLGSH LTAQAAREGR DMLALTSSQW DITDPAAAER IIRHGDVVIN
CAAYTDVDGA ESNEAVAYAV NATGPQHLAR ACARVGARLI HVSTDYVFDG DFGGAEPRPY
EPTDETAPQG VYARSKLAGE QAVLAAFPEA AVVRTAWVYT GGTGKDFVAV MRRLAAGHGR
VDVVDDQTGS PTYVADLAEA LLALADAGVR GRVLHAANEG VVSRFGQARA VFEECGADPQ
RVRPVSSAQF PRPAPRSSYS ALSSRQWALA GLTPLRHWRS ALATALAAPA NSTSIDRRLP
STRD
