SUGFT_MYCTU
ID SUGFT_MYCTU Reviewed; 234 AA.
AC P9WKZ3; L0TFA5; P65073; Q50721;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=dTDP-4-amino-4,6-dideoxyglucose formyltransferase {ECO:0000305|PubMed:28665588};
DE Short=dTDP-Qui4N formyltransferase {ECO:0000305|PubMed:28665588};
DE EC=2.1.2.- {ECO:0000269|PubMed:28665588};
DE AltName: Full=Sugar N-formyltransferase Rv3404c {ECO:0000305|PubMed:28665588};
GN OrderedLocusNames=Rv3404c; ORFNames=MTCY78.24;
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 DISRUPTION PHENOTYPE, AND FUNCTION IN VIRULENCE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12368431; DOI=10.1099/00221287-148-10-2975;
RA McAdam R.A., Quan S., Smith D.A., Bardarov S., Betts J.C., Cook F.C.,
RA Hooker E.U., Lewis A.P., Woollard P., Everett M.J., Lukey P.T.,
RA Bancroft G.J., Jacobs W.R. Jr., Duncan K.;
RT "Characterization of a Mycobacterium tuberculosis H37Rv transposon library
RT reveals insertions in 351 ORFs and mutants with altered virulence.";
RL Microbiology 148:2975-2986(2002).
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 (2.10 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP UDP, AND SUBUNIT.
RA Edwards T.E., Dranow D.M.;
RT "Crystal structure of a putative uncharacterized protein Rv3404c and likely
RT sugar N-formyltransferase from Mycobacterium tuberculosis.";
RL Submitted (MAR-2014) to the PDB data bank.
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH
RP N(5)-FORMYLTETRAHYDROFOLATE AND DTDP-4-AMINO-4,6-DIDEOXYGLUCOSE, FUNCTION,
RP CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, AND ACTIVE SITE.
RX PubMed=28665588; DOI=10.1021/acs.biochem.7b00506;
RA Dunsirn M.M., Thoden J.B., Gilbert M., Holden H.M.;
RT "Biochemical investigation of Rv3404c from Mycobacterium tuberculosis.";
RL Biochemistry 56:3818-3825(2017).
CC -!- FUNCTION: Sugar N-formyltransferase that catalyzes the conversion of
CC dTDP-4-amino-4,6-dideoxyglucose into dTDP-4-formamido-4,6-
CC dideoxyglucose using N(10)-formyltetrahydrofolate as the carbon source
CC (PubMed:28665588). Plays a role in virulence (PubMed:12368431). Has no
CC activity on dTDP-3-amino-3,6-dideoxyglucose, dTDP-3-amino-3,6-
CC dideoxygalactose, UDP-4-amino-4-deoxyarabinose, and GDP-4-amino-4,6-
CC dideoxymannose (PubMed:28665588). {ECO:0000269|PubMed:12368431,
CC ECO:0000269|PubMed:28665588}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-10-formyltetrahydrofolate + dTDP-4-amino-4,6-dideoxy-
CC alpha-D-glucose = (6S)-5,6,7,8-tetrahydrofolate + dTDP-4-formamido-
CC 4,6-dideoxy-alpha-D-glucose + H(+); Xref=Rhea:RHEA:54032,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57453, ChEBI:CHEBI:57454,
CC ChEBI:CHEBI:68501, ChEBI:CHEBI:138034;
CC Evidence={ECO:0000269|PubMed:28665588};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.08 mM for dTDP-4-amino-4,6-dideoxy-alpha-D-glucose
CC {ECO:0000269|PubMed:28665588};
CC Note=kcat is 0.9 sec(-1). {ECO:0000269|PubMed:28665588};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:28665588, ECO:0000269|Ref.5}.
CC -!- DISRUPTION PHENOTYPE: Mice infected with M.tuberculosis H37Rv mutants
CC for Rv3404c present a highly significant increase in their survival
CC time as compared with mice infected with the parental strain.
CC {ECO:0000269|PubMed:12368431}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the dTDP-Qui4N formyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46226.1; -; Genomic_DNA.
DR PIR; A70736; A70736.
DR RefSeq; NP_217921.1; NC_000962.3.
DR RefSeq; WP_003417980.1; NZ_NVQJ01000027.1.
DR PDB; 4PZU; X-ray; 2.10 A; A/B/C/D/E/F/G/H=2-234.
DR PDB; 4Q12; X-ray; 2.85 A; A/B=2-234.
DR PDB; 5VYQ; X-ray; 1.60 A; A/B=2-234.
DR PDBsum; 4PZU; -.
DR PDBsum; 4Q12; -.
DR PDBsum; 5VYQ; -.
DR AlphaFoldDB; P9WKZ3; -.
DR SMR; P9WKZ3; -.
DR STRING; 83332.Rv3404c; -.
DR PaxDb; P9WKZ3; -.
DR DNASU; 887902; -.
DR GeneID; 45427400; -.
DR GeneID; 887902; -.
DR KEGG; mtu:Rv3404c; -.
DR TubercuList; Rv3404c; -.
DR eggNOG; COG0223; Bacteria.
DR OMA; TIHEMDE; -.
DR PhylomeDB; P9WKZ3; -.
DR PHI-base; PHI:3642; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016742; F:hydroxymethyl-, formyl- and related transferase activity; IDA:UniProtKB.
DR GO; GO:0004479; F:methionyl-tRNA formyltransferase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0071951; P:conversion of methionyl-tRNA to N-formyl-methionyl-tRNA; IBA:GO_Central.
DR InterPro; IPR002376; Formyl_transf_N.
DR InterPro; IPR036477; Formyl_transf_N_sf.
DR InterPro; IPR040660; N_formyltrans_C.
DR Pfam; PF00551; Formyl_trans_N; 1.
DR Pfam; PF18216; N_formyltrans_C; 1.
DR SUPFAM; SSF53328; SSF53328; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carbohydrate metabolism; Reference proteome; Transferase.
FT CHAIN 1..234
FT /note="dTDP-4-amino-4,6-dideoxyglucose formyltransferase"
FT /id="PRO_0000014151"
FT ACT_SITE 81
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:28665588"
FT BINDING 9
FT /ligand="dTDP-4-amino-4,6-dideoxy-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:68501"
FT /evidence="ECO:0000269|PubMed:28665588,
FT ECO:0007744|PDB:5VYQ"
FT BINDING 62..64
FT /ligand="dTDP-4-amino-4,6-dideoxy-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:68501"
FT /evidence="ECO:0000269|PubMed:28665588,
FT ECO:0007744|PDB:5VYQ"
FT BINDING 65..67
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000269|PubMed:28665588,
FT ECO:0007744|PDB:5VYQ"
FT BINDING 90..94
FT /ligand="dTDP-4-amino-4,6-dideoxy-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:68501"
FT /evidence="ECO:0000269|PubMed:28665588,
FT ECO:0007744|PDB:5VYQ"
FT BINDING 112
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000269|PubMed:28665588,
FT ECO:0007744|PDB:5VYQ"
FT BINDING 116
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000269|PubMed:28665588,
FT ECO:0007744|PDB:5VYQ"
FT BINDING 175
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000269|PubMed:28665588,
FT ECO:0007744|PDB:5VYQ"
FT BINDING 209
FT /ligand="dTDP-4-amino-4,6-dideoxy-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:68501"
FT /evidence="ECO:0000269|PubMed:28665588,
FT ECO:0007744|PDB:5VYQ"
FT STRAND 3..7
FT /evidence="ECO:0007829|PDB:4PZU"
FT HELIX 10..23
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 25..30
FT /evidence="ECO:0007829|PDB:4PZU"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:4PZU"
FT HELIX 48..54
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:4PZU"
FT HELIX 69..74
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 75..83
FT /evidence="ECO:0007829|PDB:4PZU"
FT TURN 85..88
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:4PZU"
FT HELIX 93..100
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:4PZU"
FT HELIX 134..158
FT /evidence="ECO:0007829|PDB:4PZU"
FT HELIX 175..182
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:4PZU"
FT HELIX 192..201
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 210..213
FT /evidence="ECO:0007829|PDB:4PZU"
FT STRAND 219..228
FT /evidence="ECO:0007829|PDB:4PZU"
SQ SEQUENCE 234 AA; 26515 MW; 63FF857BB6FFAA8F CRC64;
MTILILTDNV HAHALAVDLQ ARHGDMDVYQ SPIGQLPGVP RCDVAERVAE IVERYDLVLS
FHCKQRFPAA LIDGVRCVNV HPGFNPYNRG WFPQVFSIID GQKVGVTIHE IDDQLDHGPI
IAQRECAIES WDSSGSVYAR LMDIERELVL EHFDAIRDGS YTAKSPATEG NLNLKKDFEQ
LRRLDLNERG TFGHFLNRLR ALTHDDFRNA WFVDASGRKV FVRVVLEPEK PAEA
