HTDY_MYCTU
ID HTDY_MYCTU Reviewed; 290 AA.
AC I6YBZ8;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=3-hydroxyacyl-thioester dehydratase Y {ECO:0000305};
DE EC=4.2.1.- {ECO:0000269|PubMed:17240207, ECO:0000269|PubMed:19136596};
DE AltName: Full=Enoyl-CoA hydratase 2 {ECO:0000305};
DE EC=4.2.1.119 {ECO:0000269|PubMed:17240207, ECO:0000269|PubMed:19136596};
GN Name=htdY {ECO:0000303|PubMed:19136596};
GN OrderedLocusNames=Rv3389c {ECO:0000312|EMBL:CCP46210.1};
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, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=H37Rv;
RX PubMed=17240207; DOI=10.1016/j.bbapap.2006.11.016;
RA Sacco E., Legendre V., Laval F., Zerbib D., Montrozier H., Eynard N.,
RA Guilhot C., Daffe M., Quemard A.;
RT "Rv3389C from Mycobacterium tuberculosis, a member of the (R)-specific
RT hydratase/dehydratase family.";
RL Biochim. Biophys. Acta 1774:303-311(2007).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19136596; DOI=10.1128/jb.01046-08;
RA Gurvitz A., Hiltunen J.K., Kastaniotis A.J.;
RT "Heterologous expression of mycobacterial proteins in Saccharomyces
RT cerevisiae reveals two physiologically functional 3-hydroxyacyl-thioester
RT dehydratases, HtdX and HtdY, in addition to HadABC and HtdZ.";
RL J. Bacteriol. 191:2683-2690(2009).
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 FUNCTION IN VIRULENCE.
RX PubMed=24907510; DOI=10.1016/j.imlet.2014.05.013;
RA Zhao J.W., Sun Z.Q., Zhang X.Y., Zhang Y., Liu J., Ye J., Chen C.C.,
RA Samten B., Wang H.H., Guo X.K., Zhang S.L.;
RT "Mycobacterial 3-hydroxyacyl-l-thioester dehydratase Y derived from
RT Mycobacterium tuberculosis induces COX-2 expression in mouse macrophages
RT through MAPK-NF-kappaB pathway.";
RL Immunol. Lett. 161:125-132(2014).
RN [6] {ECO:0007744|PDB:3KHP}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS).
RX PubMed=25613812; DOI=10.1016/j.tube.2014.12.003;
RA Baugh L., Phan I., Begley D.W., Clifton M.C., Armour B., Dranow D.M.,
RA Taylor B.M., Muruthi M.M., Abendroth J., Fairman J.W., Fox D. III,
RA Dieterich S.H., Staker B.L., Gardberg A.S., Choi R., Hewitt S.N.,
RA Napuli A.J., Myers J., Barrett L.K., Zhang Y., Ferrell M., Mundt E.,
RA Thompkins K., Tran N., Lyons-Abbott S., Abramov A., Sekar A.,
RA Serbzhinskiy D., Lorimer D., Buchko G.W., Stacy R., Stewart L.J.,
RA Edwards T.E., Van Voorhis W.C., Myler P.J.;
RT "Increasing the structural coverage of tuberculosis drug targets.";
RL Tuberculosis 95:142-148(2015).
CC -!- FUNCTION: Shows trans-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydratase
CC activity (PubMed:17240207). In vitro, can hydrate various enoyl-CoA
CC such as (2E)-hexenoyl-CoA, (2E)-octenoyl-CoA, (2E)-decenoyl-CoA, (2E)-
CC dodecenoyl-CoA and (2E)-hexadecenoyl-CoA (PubMed:17240207,
CC PubMed:19136596). May contribute to the persistence of the tuberculosis
CC infection by inducing COX-2 expression in macrophages through MAPK-NF-
CC kappaB signaling pathway (PubMed:24907510).
CC {ECO:0000269|PubMed:17240207, ECO:0000269|PubMed:19136596,
CC ECO:0000269|PubMed:24907510}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:26526, ChEBI:CHEBI:15377, ChEBI:CHEBI:57319,
CC ChEBI:CHEBI:58856; EC=4.2.1.119;
CC Evidence={ECO:0000269|PubMed:17240207, ECO:0000269|PubMed:19136596};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexanoyl-CoA = (2E)-hexenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:46720, ChEBI:CHEBI:15377, ChEBI:CHEBI:62077,
CC ChEBI:CHEBI:74280; Evidence={ECO:0000269|PubMed:19136596};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-octenoyl-CoA + H2O = (3R)-hydroxyoctanoyl-CoA;
CC Xref=Rhea:RHEA:40187, ChEBI:CHEBI:15377, ChEBI:CHEBI:62242,
CC ChEBI:CHEBI:74279; Evidence={ECO:0000269|PubMed:17240207};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-3-hydroxydecanoyl-CoA = (2E)-decenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:45992, ChEBI:CHEBI:15377, ChEBI:CHEBI:61406,
CC ChEBI:CHEBI:74272; Evidence={ECO:0000269|PubMed:17240207,
CC ECO:0000269|PubMed:19136596};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-3-hydroxydodecanoyl-CoA = (2E)-dodecenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:44024, ChEBI:CHEBI:15377, ChEBI:CHEBI:57330,
CC ChEBI:CHEBI:74276; Evidence={ECO:0000269|PubMed:17240207};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:39159, ChEBI:CHEBI:15377, ChEBI:CHEBI:61526,
CC ChEBI:CHEBI:74278; Evidence={ECO:0000269|PubMed:17240207};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.6 uM for dodecenoyl-CoA {ECO:0000269|PubMed:17240207};
CC Note=kcat is 45 sec(-1) with dodecenoyl-CoA as substrate.
CC {ECO:0000269|PubMed:17240207};
CC -!- SIMILARITY: Belongs to the enoyl-CoA hydratase/isomerase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46210.1; -; Genomic_DNA.
DR RefSeq; NP_217906.1; NC_000962.3.
DR RefSeq; WP_003417929.1; NZ_NVQJ01000027.1.
DR PDB; 3KHP; X-ray; 2.30 A; A/B/C/D=1-290.
DR PDBsum; 3KHP; -.
DR AlphaFoldDB; I6YBZ8; -.
DR SMR; I6YBZ8; -.
DR STRING; 83332.Rv3389c; -.
DR SwissLipids; SLP:000001166; -.
DR PaxDb; I6YBZ8; -.
DR PRIDE; I6YBZ8; -.
DR DNASU; 887923; -.
DR GeneID; 887923; -.
DR KEGG; mtu:Rv3389c; -.
DR PATRIC; fig|83332.111.peg.3777; -.
DR TubercuList; Rv3389c; -.
DR eggNOG; COG2030; Bacteria.
DR OMA; IACSPFA; -.
DR PhylomeDB; I6YBZ8; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; IBA:GO_Central.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
DR InterPro; IPR029069; HotDog_dom_sf.
DR InterPro; IPR002539; MaoC-like_dom.
DR Pfam; PF01575; MaoC_dehydratas; 1.
DR SUPFAM; SSF54637; SSF54637; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Fatty acid metabolism; Lipid metabolism; Lyase;
KW Reference proteome.
FT CHAIN 1..290
FT /note="3-hydroxyacyl-thioester dehydratase Y"
FT /id="PRO_0000448720"
FT DOMAIN 161..271
FT /note="MaoC-like"
FT /evidence="ECO:0000255"
FT REGION 147..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT STRAND 15..19
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 21..30
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 38..41
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 64..69
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 93..108
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 115..124
FT /evidence="ECO:0007829|PDB:3KHP"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 131..141
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 177..181
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 194..199
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 210..224
FT /evidence="ECO:0007829|PDB:3KHP"
FT TURN 225..228
FT /evidence="ECO:0007829|PDB:3KHP"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 233..240
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 250..258
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 261..268
FT /evidence="ECO:0007829|PDB:3KHP"
FT STRAND 277..287
FT /evidence="ECO:0007829|PDB:3KHP"
SQ SEQUENCE 290 AA; 30296 MW; F2A2556DFC491126 CRC64;
MAIDPNSIGA VTEPMLFEWT DRDTLLYAIG VGAGTGDLAF TTENSHGIDQ QVLPTYAVIC
CPAFGAAAKV GTFNPAALLH GSQGIRLHAP LPAAGKLSVV TEVADIQDKG EGKNAIVVLR
GRGCDPESGS LVAETLTTLV LRGQGGFGGA RGERPAAPEF PDRHPDARID MPTREDQALI
YRLSGDRNPL HSDPWFATQL AGFPKPILHG LCTYGVAGRA LVAELGGGVA ANITSIAARF
TKPVFPGETL STVIWRTEPG RAVFRTEVAG SDGAEARVVL DDGAVEYVAG
