RMLC_MYCTU
ID RMLC_MYCTU Reviewed; 202 AA.
AC P9WH11; L0TE75; O06330; Q7D5I3;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=dTDP-4-dehydrorhamnose 3,5-epimerase {ECO:0000305};
DE EC=5.1.3.13 {ECO:0000269|PubMed:16472764};
DE AltName: Full=Thymidine diphospho-4-keto-rhamnose 3,5-epimerase {ECO:0000305};
DE AltName: Full=dTDP-4-keto-6-deoxyglucose 3,5-epimerase {ECO:0000303|PubMed:15103135};
DE AltName: Full=dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase {ECO:0000303|PubMed:12951098};
DE AltName: Full=dTDP-L-rhamnose synthase {ECO:0000305};
GN Name=rmlC; Synonyms=strM; OrderedLocusNames=Rv3465;
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 CATALYTIC ACTIVITY.
RX PubMed=16472764; DOI=10.1016/j.bbrc.2006.01.130;
RA Li W., Xin Y., McNeil M.R., Ma Y.;
RT "rmlB and rmlC genes are essential for growth of mycobacteria.";
RL Biochem. Biophys. Res. Commun. 342:170-178(2006).
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).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG, AND
RP SUBUNIT.
RX PubMed=12951098; DOI=10.1016/s0960-894x(03)00673-5;
RA Babaoglu K., Page M.A., Jones V.C., McNeil M.R., Dong C., Naismith J.H.,
RA Lee R.E.;
RT "Novel inhibitors of an emerging target in Mycobacterium tuberculosis;
RT substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis.";
RL Bioorg. Med. Chem. Lett. 13:3227-3230(2003).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), AND SUBUNIT.
RX PubMed=15103135; DOI=10.1107/s0907444904005323;
RA Kantardjieff K.A., Kim C.Y., Naranjo C., Waldo G.S., Lekin T.,
RA Segelke B.W., Zemla A., Park M.S., Terwilliger T.C., Rupp B.;
RT "Mycobacterium tuberculosis RmlC epimerase (Rv3465): a promising drug-
RT target structure in the rhamnose pathway.";
RL Acta Crystallogr. D 60:895-902(2004).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP REACTION MECHANISM, AND SUBUNIT.
RX PubMed=17046787; DOI=10.1016/j.jmb.2006.09.063;
RA Dong C., Major L.L., Srikannathasan V., Errey J.C., Giraud M.F., Lam J.S.,
RA Graninger M., Messner P., McNeil M.R., Field R.A., Whitfield C.,
RA Naismith J.H.;
RT "RmlC, a C3' and C5' carbohydrate epimerase, appears to operate via an
RT intermediate with an unusual twist boat conformation.";
RL J. Mol. Biol. 365:146-159(2007).
CC -!- FUNCTION: Catalyzes the epimerization of the C3' and C5'positions of
CC dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose.
CC Involved in the biosynthesis of the dTDP-L-rhamnose which is a
CC 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.
CC {ECO:0000269|PubMed:16472764}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dTDP-4-dehydro-6-deoxy-alpha-D-glucose = dTDP-4-dehydro-beta-
CC L-rhamnose; Xref=Rhea:RHEA:16969, ChEBI:CHEBI:57649,
CC ChEBI:CHEBI:62830; EC=5.1.3.13;
CC Evidence={ECO:0000269|PubMed:16472764};
CC -!- PATHWAY: Carbohydrate biosynthesis; dTDP-L-rhamnose biosynthesis.
CC {ECO:0000250|UniProtKB:P26394}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12951098,
CC ECO:0000269|PubMed:15103135, ECO:0000269|PubMed:17046787}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the dTDP-4-dehydrorhamnose 3,5-epimerase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46287.1; -; Genomic_DNA.
DR PIR; F70566; F70566.
DR RefSeq; NP_217982.1; NC_000962.3.
DR RefSeq; WP_003418610.1; NZ_NVQJ01000091.1.
DR PDB; 1PM7; X-ray; 2.20 A; A/B=1-202.
DR PDB; 1UPI; X-ray; 1.70 A; A=1-202.
DR PDB; 2IXC; X-ray; 1.79 A; A/B/C/D=1-202.
DR PDBsum; 1PM7; -.
DR PDBsum; 1UPI; -.
DR PDBsum; 2IXC; -.
DR AlphaFoldDB; P9WH11; -.
DR SMR; P9WH11; -.
DR STRING; 83332.Rv3465; -.
DR ChEMBL; CHEMBL3883301; -.
DR DrugBank; DB04530; S,S-(2-Hydroxyethyl)Thiocysteine.
DR PaxDb; P9WH11; -.
DR DNASU; 887352; -.
DR GeneID; 887352; -.
DR KEGG; mtu:Rv3465; -.
DR TubercuList; Rv3465; -.
DR eggNOG; COG1898; Bacteria.
DR OMA; RGVFLEW; -.
DR PhylomeDB; P9WH11; -.
DR BRENDA; 5.1.3.13; 3445.
DR UniPathway; UPA00124; -.
DR PRO; PR:P9WH11; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0008830; F:dTDP-4-dehydrorhamnose 3,5-epimerase activity; IDA:MTBBASE.
DR GO; GO:0016854; F:racemase and epimerase activity; IBA:GO_Central.
DR GO; GO:0033692; P:cellular polysaccharide biosynthetic process; IBA:GO_Central.
DR GO; GO:0019305; P:dTDP-rhamnose biosynthetic process; IDA:MTBBASE.
DR GO; GO:0045226; P:extracellular polysaccharide biosynthetic process; IGI:UniProtKB.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR000888; dTDP_sugar_isom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR PANTHER; PTHR21047; PTHR21047; 1.
DR Pfam; PF00908; dTDP_sugar_isom; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
DR TIGRFAMs; TIGR01221; rmlC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carbohydrate metabolism; Isomerase; Reference proteome.
FT CHAIN 1..202
FT /note="dTDP-4-dehydrorhamnose 3,5-epimerase"
FT /id="PRO_0000395349"
FT ACT_SITE 62
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:17046787,
FT ECO:0007744|PDB:2IXC"
FT ACT_SITE 132
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9HU21"
FT BINDING 23
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17046787,
FT ECO:0007744|PDB:2IXC"
FT BINDING 28
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17046787,
FT ECO:0007744|PDB:2IXC"
FT BINDING 47..49
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:17046787,
FT ECO:0007744|PDB:2IXC"
FT BINDING 59
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17046787,
FT ECO:0007744|PDB:2IXC"
FT BINDING 72
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17046787,
FT ECO:0000305|PubMed:12951098, ECO:0007744|PDB:1PM7"
FT BINDING 119
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17046787,
FT ECO:0000305|PubMed:12951098, ECO:0007744|PDB:1PM7,
FT ECO:0007744|PDB:2IXC"
FT BINDING 143
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9HU21"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9HU21"
FT SITE 138
FT /note="Participates in a stacking interaction with the
FT thymidine ring of dTDP-4-oxo-6-deoxyglucose"
FT /evidence="ECO:0000250|UniProtKB:Q5SFD1"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 11..15
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 24..27
FT /evidence="ECO:0007829|PDB:1UPI"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:1UPI"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 72..86
FT /evidence="ECO:0007829|PDB:1UPI"
FT TURN 93..96
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 98..104
FT /evidence="ECO:0007829|PDB:1UPI"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 125..136
FT /evidence="ECO:0007829|PDB:1UPI"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:1UPI"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:1UPI"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:2IXC"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:1UPI"
FT HELIX 177..182
FT /evidence="ECO:0007829|PDB:1UPI"
FT HELIX 189..199
FT /evidence="ECO:0007829|PDB:1UPI"
SQ SEQUENCE 202 AA; 22314 MW; A6A1AFA0FC0F5871 CRC64;
MKARELDVPG AWEITPTIHV DSRGLFFEWL TDHGFRAFAG HSLDVRQVNC SVSSAGVLRG
LHFAQLPPSQ AKYVTCVSGS VFDVVVDIRE GSPTFGRWDS VLLDDQDRRT IYVSEGLAHG
FLALQDNSTV MYLCSAEYNP QREHTICATD PTLAVDWPLV DGAAPSLSDR DAAAPSFEDV
RASGLLPRWE QTQRFIGEMR GT
