ATSK_MYCTU
ID ATSK_MYCTU Reviewed; 295 AA.
AC P9WKZ1; L0TCF8; P65075; Q50719;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Alpha-ketoglutarate-dependent sulfate ester dioxygenase {ECO:0000303|PubMed:23762287};
DE EC=1.14.11.- {ECO:0000269|PubMed:23762287, ECO:0000269|PubMed:25427196};
DE AltName: Full=Type II alkyl sulfatase {ECO:0000303|PubMed:23762287};
GN OrderedLocusNames=Rv3406; ORFNames=MTCY78.22c;
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 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 [4]
RP INDUCTION.
RC STRAIN=H37Rv;
RX PubMed=29395080; DOI=10.1016/j.bbrc.2018.01.152;
RA Gopalan A., Bhagavat R., Chandra N., Subbarao S.H., Raja A.,
RA Bethunaickan R.;
RT "Biophysical and biochemical characterization of Rv3405c, a tetracycline
RT repressor protein from Mycobacterium tuberculosis.";
RL Biochem. Biophys. Res. Commun. 496:799-805(2018).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP DISRUPTION PHENOTYPE, COFACTOR, AND SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman, and H37Rv;
RX PubMed=23762287; DOI=10.1371/journal.pone.0065080;
RA Sogi K.M., Gartner Z.J., Breidenbach M.A., Appel M.J., Schelle M.W.,
RA Bertozzi C.R.;
RT "Mycobacterium tuberculosis Rv3406 is a type II alkyl sulfatase capable of
RT sulfate scavenging.";
RL PLoS ONE 8:E65080-E65080(2013).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH IRON ION, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND INDUCTION.
RX PubMed=25427196; DOI=10.1021/cb5007163;
RA Neres J., Hartkoorn R.C., Chiarelli L.R., Gadupudi R., Pasca M.R., Mori G.,
RA Venturelli A., Savina S., Makarov V., Kolly G.S., Molteni E., Binda C.,
RA Dhar N., Ferrari S., Brodin P., Delorme V., Landry V.,
RA de Jesus Lopes Ribeiro A.L., Farina D., Saxena P., Pojer F., Carta A.,
RA Luciani R., Porta A., Zanoni G., De Rossi E., Costi M.P., Riccardi G.,
RA Cole S.T.;
RT "2-Carboxyquinoxalines kill Mycobacterium tuberculosis through noncovalent
RT inhibition of DprE1.";
RL ACS Chem. Biol. 10:705-714(2015).
CC -!- FUNCTION: Alpha-ketoglutarate-dependent sulfate ester dioxygenase,
CC which oxidizes medium-chain alkyl-sulfate esters (PubMed:23762287).
CC Shows preference for 2-ethylhexyl sulfate (2-EHS) in vitro, leading to
CC the formation of succinate and 2-ethylhexanal (PubMed:23762287,
CC PubMed:25427196). Has likely a role in sulfate scavenging in vivo
CC (PubMed:23762287). {ECO:0000269|PubMed:23762287,
CC ECO:0000269|PubMed:25427196}.
CC -!- FUNCTION: Also causes the inactivation of the 2-carboxyquinoxaline
CC Ty38c (an antitubercular compound that inhibits DprE1) via oxidative
CC decarboxylation, using Ty38c instead of alpha-ketoglutarate as a
CC substrate. Is thus responsible for primary resistance of M.tuberculosis
CC to Ty38c in vitro. Overexpression of Rv3406 causes resistance to Ty38c.
CC {ECO:0000269|PubMed:25427196}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-ethylhexyl sulfate + 2-oxoglutarate + O2 = 2-ethylhexanal +
CC CO2 + H(+) + succinate + sulfate; Xref=Rhea:RHEA:47620,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16189,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:87808, ChEBI:CHEBI:87809;
CC Evidence={ECO:0000269|PubMed:23762287, ECO:0000269|PubMed:25427196};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:23762287, ECO:0000269|PubMed:25427196};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.8 uM for 2-EHS (at pH 7 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:25427196};
CC KM=9.4 uM for alpha-ketoglutarate (at pH 7 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:25427196};
CC KM=160 uM for Ty38c (at pH 7 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:25427196};
CC Note=kcat is 21.8 min(-1) with alpha-ketoglutarate and 2-EHS as
CC substrates (at pH 7 and 25 degrees Celsius). kcat is 1.54 min(-1) for
CC the oxidative decarboxylation of Ty38c (at pH 7 and 25 degrees
CC Celsius). {ECO:0000269|PubMed:25427196};
CC -!- INDUCTION: Repressed by the transcriptional repressor Rv3405c.
CC {ECO:0000269|PubMed:25427196, ECO:0000269|PubMed:29395080}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not replicate in
CC minimal media with 2-ethyl hexyl sulfate as the sole sulfur source, in
CC contrast to wild-type. {ECO:0000269|PubMed:23762287}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the TfdA dioxygenase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46228.1; -; Genomic_DNA.
DR PIR; C70736; C70736.
DR RefSeq; NP_217923.1; NC_000962.3.
DR RefSeq; WP_003900050.1; NZ_NVQJ01000027.1.
DR PDB; 4CVY; X-ray; 2.00 A; A/B/C/D=1-295.
DR PDB; 4FFA; X-ray; 2.50 A; A/B/C/D=1-295.
DR PDBsum; 4CVY; -.
DR PDBsum; 4FFA; -.
DR AlphaFoldDB; P9WKZ1; -.
DR SMR; P9WKZ1; -.
DR STRING; 83332.Rv3406; -.
DR PaxDb; P9WKZ1; -.
DR DNASU; 887955; -.
DR GeneID; 45427402; -.
DR GeneID; 887955; -.
DR KEGG; mtu:Rv3406; -.
DR TubercuList; Rv3406; -.
DR eggNOG; COG2175; Bacteria.
DR OMA; FVDAYPK; -.
DR PhylomeDB; P9WKZ1; -.
DR BioCyc; MetaCyc:G185E-7683-MON; -.
DR BRENDA; 1.14.11.77; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.60.130.10; -; 1.
DR InterPro; IPR042098; TauD-like_sf.
DR InterPro; IPR003819; TauD/TfdA-like.
DR Pfam; PF02668; TauD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Dioxygenase; Iron; Metal-binding;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..295
FT /note="Alpha-ketoglutarate-dependent sulfate ester
FT dioxygenase"
FT /id="PRO_0000104125"
FT BINDING 71
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9WWU5"
FT BINDING 98
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:25427196"
FT BINDING 100
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:25427196"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9WWU5"
FT BINDING 125
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9WWU5"
FT BINDING 252
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:25427196"
FT BINDING 263
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9WWU5"
FT BINDING 267
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9WWU5"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 11..14
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 16..20
FT /evidence="ECO:0007829|PDB:4CVY"
FT HELIX 29..42
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:4CVY"
FT HELIX 55..63
FT /evidence="ECO:0007829|PDB:4CVY"
FT TURN 100..103
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 109..117
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:4CVY"
FT HELIX 130..135
FT /evidence="ECO:0007829|PDB:4CVY"
FT HELIX 139..146
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 181..189
FT /evidence="ECO:0007829|PDB:4CVY"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:4CVY"
FT HELIX 212..227
FT /evidence="ECO:0007829|PDB:4CVY"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:4CVY"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:4CVY"
SQ SEQUENCE 295 AA; 32579 MW; 213EB93DEF58F2A6 CRC64;
MTDLITVKKL GSRIGAQIDG VRLGGDLDPA AVNEIRAALL AHKVVFFRGQ HQLDDAEQLA
FAGLLGTPIG HPAAIALADD APIITPINSE FGKANRWHTD VTFAANYPAA SVLRAVSLPS
YGGSTLWANT AAAYAELPEP LKCLTENLWA LHTNRYDYVT TKPLTAAQRA FRQVFEKPDF
RTEHPVVRVH PETGERTLLA GDFVRSFVGL DSHESRVLFE VLQRRITMPE NTIRWNWAPG
DVAIWDNRAT QHRAIDDYDD QHRLMHRVTL MGDVPVDVYG QASRVISGAP MEIAG
