RMLD_SALTY
ID RMLD_SALTY Reviewed; 299 AA.
AC P26392;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=dTDP-4-dehydrorhamnose reductase {ECO:0000305};
DE EC=1.1.1.133 {ECO:0000269|PubMed:12057193};
DE AltName: Full=dTDP-4-keto-L-rhamnose reductase {ECO:0000305};
DE AltName: Full=dTDP-6-deoxy-L-lyxo-4-hexulose reductase {ECO:0000303|PubMed:12057193};
DE AltName: Full=dTDP-6-deoxy-L-mannose dehydrogenase {ECO:0000305};
DE AltName: Full=dTDP-L-rhamnose synthase {ECO:0000305};
GN Name=rfbD; Synonyms=rmlD; OrderedLocusNames=STM2096;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=LT2;
RX PubMed=1710759; DOI=10.1111/j.1365-2958.1991.tb00741.x;
RA Jiang X.-M., Neal B., Santiago F., Lee S.J., Romana L.K., Reeves P.R.;
RT "Structure and sequence of the rfb (O antigen) gene cluster of Salmonella
RT serovar typhimurium (strain LT2).";
RL Mol. Microbiol. 5:695-713(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3] {ECO:0007744|PDB:1KBZ, ECO:0007744|PDB:1KC1, ECO:0007744|PDB:1KC3, ECO:0007744|PDB:1N2S}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEXES WITH NADH, NADPH AND
RP DTDP-L-RHAMNOSE, FUNCTION IN DTDP-RHAMNOSE BIOSYNTHESIS, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF VAL-67; ASP-68;
RP THR-104; TYR-128 AND TRP-153, COFACTOR, ACTIVE SITE, REACTION MECHANISM,
RP AND SUBUNIT.
RX PubMed=12057193; DOI=10.1016/s0969-2126(02)00770-0;
RA Blankenfeldt W., Kerr I.D., Giraud M.F., McMiken H.J., Leonard G.,
RA Whitfield C., Messner P., Graninger M., Naismith J.H.;
RT "Variation on a theme of SDR. dTDP-6-deoxy-L- lyxo-4-hexulose reductase
RT (RmlD) shows a new Mg2+-dependent dimerization mode.";
RL Structure 10:773-786(2002).
CC -!- FUNCTION: Involved in the biosynthesis of the dTDP-L-rhamnose which is
CC an important component of lipopolysaccharide (LPS). Catalyzes the
CC reduction of dTDP-6-deoxy-L-lyxo-4-hexulose to yield dTDP-L-rhamnose.
CC RmlD uses NADH and NADPH nearly equally well.
CC {ECO:0000269|PubMed:12057193}.
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:0000269|PubMed:12057193};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12057193};
CC Note=Binds 1 Mg(2+) ion per monomer. Mg(2+) is important for
CC dimerization. {ECO:0000269|PubMed:12057193};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.11 mM for dTDP-6-deoxy-L-mannose (at pH 6.5)
CC {ECO:0000269|PubMed:12057193};
CC -!- PATHWAY: Carbohydrate biosynthesis; dTDP-L-rhamnose biosynthesis.
CC {ECO:0000250|UniProtKB:P37760}.
CC -!- PATHWAY: Bacterial outer membrane biogenesis; LPS O-antigen
CC biosynthesis. {ECO:0000250|UniProtKB:P37760}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12057193}.
CC -!- SIMILARITY: Belongs to the dTDP-4-dehydrorhamnose reductase family.
CC {ECO:0000305}.
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DR EMBL; X56793; CAA40116.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL21000.1; -; Genomic_DNA.
DR PIR; S15300; S15300.
DR RefSeq; NP_461041.1; NC_003197.2.
DR RefSeq; WP_001023662.1; NC_003197.2.
DR PDB; 1KBZ; X-ray; 2.20 A; A=1-299.
DR PDB; 1KC1; X-ray; 2.60 A; A=1-299.
DR PDB; 1KC3; X-ray; 2.70 A; A=1-299.
DR PDB; 1N2S; X-ray; 2.00 A; A=1-299.
DR PDBsum; 1KBZ; -.
DR PDBsum; 1KC1; -.
DR PDBsum; 1KC3; -.
DR PDBsum; 1N2S; -.
DR AlphaFoldDB; P26392; -.
DR SMR; P26392; -.
DR STRING; 99287.STM2096; -.
DR DrugBank; DB03723; 2'-Deoxy-thymidine-beta-L-rhamnose.
DR PaxDb; P26392; -.
DR EnsemblBacteria; AAL21000; AAL21000; STM2096.
DR GeneID; 1253617; -.
DR KEGG; stm:STM2096; -.
DR PATRIC; fig|99287.12.peg.2218; -.
DR HOGENOM; CLU_045518_1_2_6; -.
DR OMA; AGETTWH; -.
DR PhylomeDB; P26392; -.
DR BioCyc; SENT99287:STM2096-MON; -.
DR SABIO-RK; P26392; -.
DR UniPathway; UPA00124; -.
DR UniPathway; UPA00281; -.
DR EvolutionaryTrace; P26392; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0008831; F:dTDP-4-dehydrorhamnose reductase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019305; P:dTDP-rhamnose biosynthetic process; IBA:GO_Central.
DR GO; GO:0045226; P:extracellular polysaccharide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009103; P:lipopolysaccharide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009243; P:O antigen biosynthetic process; IEA:UniProtKB-UniPathway.
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 3D-structure; Carbohydrate metabolism; Lipopolysaccharide biosynthesis;
KW Magnesium; Metal-binding; NAD; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..299
FT /note="dTDP-4-dehydrorhamnose reductase"
FT /id="PRO_0000207986"
FT ACT_SITE 128
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:12057193"
FT BINDING 10..12
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1N2S"
FT BINDING 11..12
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1KC1"
FT BINDING 30
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1N2S"
FT BINDING 39..40
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1N2S"
FT BINDING 39..40
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1KC1"
FT BINDING 63..65
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1N2S"
FT BINDING 63..65
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1KC1"
FT BINDING 102
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1KC1"
FT BINDING 104..105
FT /ligand="dTDP-beta-L-rhamnose"
FT /ligand_id="ChEBI:CHEBI:57510"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1KC3"
FT BINDING 128
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1N2S"
FT BINDING 128
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1KC1"
FT BINDING 132
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1N2S"
FT BINDING 132
FT /ligand="NADPH"
FT /ligand_id="ChEBI:CHEBI:57783"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1KC1"
FT BINDING 153
FT /ligand="dTDP-beta-L-rhamnose"
FT /ligand_id="ChEBI:CHEBI:57510"
FT /evidence="ECO:0000269|PubMed:12057193,
FT ECO:0007744|PDB:1KC3"
FT SITE 104
FT /note="Could provide a fine-tuning to achieve optimal pKa
FT matching between active site and substrate"
FT /evidence="ECO:0000305|PubMed:12057193"
FT MUTAGEN 67
FT /note="V->A: Significantly reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:12057193"
FT MUTAGEN 68
FT /note="D->A: Slightly reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:12057193"
FT MUTAGEN 104
FT /note="T->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12057193"
FT MUTAGEN 128
FT /note="Y->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12057193"
FT MUTAGEN 153
FT /note="W->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12057193"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 11..19
FT /evidence="ECO:0007829|PDB:1N2S"
FT TURN 20..23
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 24..29
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 67..70
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 74..81
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 83..92
FT /evidence="ECO:0007829|PDB:1N2S"
FT TURN 93..96
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 98..104
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:1KC1"
FT HELIX 127..142
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 144..151
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 162..172
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 189..205
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 223..237
FT /evidence="ECO:0007829|PDB:1N2S"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:1KC3"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:1KC3"
FT HELIX 269..275
FT /evidence="ECO:0007829|PDB:1N2S"
FT HELIX 282..294
FT /evidence="ECO:0007829|PDB:1N2S"
SQ SEQUENCE 299 AA; 32554 MW; ABAA0476AF5ECDE7 CRC64;
MNILLFGKTG QVGWELQRSL APVGNLIALD VHSKEFCGDF SNPKGVAETV RKLRPDVIVN
AAAHTAVDKA ESEPELAQLL NATSVEAIAK AANETGAWVV HYSTDYVFPG TGDIPWQETD
ATSPLNVYGK TKLAGEKALQ DNCPKHLIFR TSWVYAGKGN NFAKTMLRLA KERQTLSVIN
DQYGAPTGAE LLADCTAHAI RVALNKPEVA GLYHLVAGGT TTWHDYAALV FDEARKAGIT
LALTELNAVP TSAYPTPASR PGNSRLNTEK FQRNFDLILP QWELGVKRML TEMFTTTTI
