HSAD_MYCTU
ID HSAD_MYCTU Reviewed; 291 AA.
AC P9WNH5; L0TEJ3; P96851; Q7D596;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=4,5:9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase;
DE EC=3.7.1.17;
DE AltName: Full=2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase;
DE Short=HOPDA hydrolase;
DE EC=3.7.1.8;
DE AltName: Full=Meta-cleavage product hydrolase;
DE Short=MCP hydrolase;
GN Name=hsaD; Synonyms=bphD; OrderedLocusNames=Rv3569c;
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 INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17635188; DOI=10.1111/j.1365-2958.2007.05827.x;
RA Kendall S.L., Withers M., Soffair C.N., Moreland N.J., Gurcha S.,
RA Sidders B., Frita R., Ten Bokum A., Besra G.S., Lott J.S., Stoker N.G.;
RT "A highly conserved transcriptional repressor controls a large regulon
RT involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium
RT tuberculosis.";
RL Mol. Microbiol. 65:684-699(2007).
RN [3]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17264217; DOI=10.1073/pnas.0605728104;
RA Van der Geize R., Yam K., Heuser T., Wilbrink M.H., Hara H., Anderton M.C.,
RA Sim E., Dijkhuizen L., Davies J.E., Mohn W.W., Eltis L.D.;
RT "A gene cluster encoding cholesterol catabolism in a soil actinomycete
RT provides insight into Mycobacterium tuberculosis survival in macrophages.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1947-1952(2007).
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 (2.35 ANGSTROMS), AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18097091; DOI=10.1107/s1744309107065931;
RA Lack N., Lowe E.D., Liu J., Eltis L.D., Noble M.E., Sim E., Westwood I.M.;
RT "Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium
RT tuberculosis.";
RL Acta Crystallogr. F 64:2-7(2008).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT SER-114 IN COMPLEX WITH
RP SUBSTRATE ANALOGS, FUNCTION AS A HYDROLASE, CATALYTIC ACTIVITY, MUTAGENESIS
RP OF SER-114, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBUNIT.
RX PubMed=19875455; DOI=10.1074/jbc.m109.058081;
RA Lack N.A., Yam K.C., Lowe E.D., Horsman G.P., Owen R.L., Sim E.,
RA Eltis L.D.;
RT "Characterization of a carbon-carbon hydrolase from Mycobacterium
RT tuberculosis involved in cholesterol metabolism.";
RL J. Biol. Chem. 285:434-443(2010).
CC -!- FUNCTION: Catalyzes the hydrolysis of a carbon-carbon bond in 4,5:
CC 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate (4,9-
CC DSHA) to yield 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate
CC (DOHNAA) and 2-hydroxy-hexa-2,4-dienoate (HHD). Is also able to
CC catalyze the hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic
CC acid (HOPDA) and the synthetic analog 8-(2-chlorophenyl)-2-hydroxy-5-
CC methyl-6-oxoocta-2,4-dienoic acid (HOPODA).
CC {ECO:0000269|PubMed:19875455}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(1E,2Z)-3-hydroxy-5,9,17-trioxo-4,5:9,10-disecoandrosta-
CC 1(10),2-dien-4-oate + H2O = (2Z,4Z)-2-hydroxyhexa-2,4-dienoate + 3-
CC [(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate
CC + H(+); Xref=Rhea:RHEA:32035, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:63690, ChEBI:CHEBI:63692, ChEBI:CHEBI:63693; EC=3.7.1.17;
CC Evidence={ECO:0000269|PubMed:19875455};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2,6-dioxo-6-phenylhexa-3-enoate + H2O = 2-oxopent-4-enoate +
CC benzoate + H(+); Xref=Rhea:RHEA:17161, ChEBI:CHEBI:11641,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16150,
CC ChEBI:CHEBI:64675; EC=3.7.1.8;
CC Evidence={ECO:0000269|PubMed:19875455};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8 uM for 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (at pH 7.5
CC and at 25 degrees Celsius) {ECO:0000269|PubMed:17264217,
CC ECO:0000269|PubMed:19875455};
CC KM=17 uM for 4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-
CC diene-4-oic acid (4,9-DSHA) (at pH 7.5 and at 25 degrees Celsius)
CC {ECO:0000269|PubMed:17264217, ECO:0000269|PubMed:19875455};
CC KM=310 uM for 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-
CC dienoic acid (at pH 7.5 and at 25 degrees Celsius)
CC {ECO:0000269|PubMed:17264217, ECO:0000269|PubMed:19875455};
CC Vmax=0.06 umol/sec/mg enzyme with 4,9-DSHA as substrate (at pH 8 and
CC at 25 degrees Celsius) {ECO:0000269|PubMed:17264217,
CC ECO:0000269|PubMed:19875455};
CC Vmax=0.009 umol/sec/mg enzyme with 2-hydroxy-6-oxo-6-phenylhexa-2,4-
CC dienoic acid as substrate (at pH 8 and at 25 degrees Celsius)
CC {ECO:0000269|PubMed:17264217, ECO:0000269|PubMed:19875455};
CC -!- PATHWAY: Lipid metabolism; steroid biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18097091,
CC ECO:0000269|PubMed:19875455}.
CC -!- INDUCTION: Induced by KstR. {ECO:0000269|PubMed:17635188}.
CC -!- MISCELLANEOUS: Cholesterol metabolism contributes to the survival of
CC M.tuberculosis in the host by helping the bacterial multiplication
CC during earlier stages of infection and to the dissemination of the
CC pathogen in the host.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. HsaD family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46392.1; -; Genomic_DNA.
DR PIR; G70605; G70605.
DR RefSeq; NP_218086.1; NC_000962.3.
DR RefSeq; WP_003419381.1; NZ_NVQJ01000014.1.
DR PDB; 2VF2; X-ray; 2.35 A; A/B=1-291.
DR PDB; 2WUD; X-ray; 2.10 A; A/B=1-291.
DR PDB; 2WUE; X-ray; 1.80 A; A/B=1-291.
DR PDB; 2WUF; X-ray; 1.90 A; A/B=1-291.
DR PDB; 2WUG; X-ray; 1.80 A; A/B=1-291.
DR PDB; 5JZB; X-ray; 2.10 A; A/B=7-288.
DR PDB; 5JZS; X-ray; 2.27 A; A/B=7-290.
DR PDBsum; 2VF2; -.
DR PDBsum; 2WUD; -.
DR PDBsum; 2WUE; -.
DR PDBsum; 2WUF; -.
DR PDBsum; 2WUG; -.
DR PDBsum; 5JZB; -.
DR PDBsum; 5JZS; -.
DR AlphaFoldDB; P9WNH5; -.
DR SMR; P9WNH5; -.
DR STRING; 83332.Rv3569c; -.
DR DrugBank; DB07911; (3E)-2,6-DIOXO-6-PHENYLHEX-3-ENOATE.
DR SwissLipids; SLP:000001006; -.
DR ESTHER; myctu-Rv3569c; Carbon-carbon_bond_hydrolase.
DR PaxDb; P9WNH5; -.
DR DNASU; 887378; -.
DR GeneID; 887378; -.
DR KEGG; mtu:Rv3569c; -.
DR TubercuList; Rv3569c; -.
DR eggNOG; COG2267; Bacteria.
DR OMA; VYILENC; -.
DR PhylomeDB; P9WNH5; -.
DR BioCyc; MetaCyc:G185E-7847-MON; -.
DR BRENDA; 3.7.1.8; 3445.
DR SABIO-RK; P9WNH5; -.
DR UniPathway; UPA00062; -.
DR PRO; PR:P9WNH5; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0018774; F:2,6-dioxo-6-phenylhexa-3-enoate hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0102296; F:4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0034820; F:4,9-DSHA hydrolase activity; IDA:MTBBASE.
DR GO; GO:0019439; P:aromatic compound catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR PRINTS; PR00111; ABHYDROLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aromatic hydrocarbons catabolism; Hydrolase;
KW Lipid degradation; Lipid metabolism; Reference proteome.
FT CHAIN 1..291
FT /note="4,5:9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-
FT 1(10),2-diene-4-oate hydrolase"
FT /id="PRO_0000404509"
FT ACT_SITE 269
FT /note="Proton acceptor"
FT BINDING 45..46
FT /ligand="substrate"
FT BINDING 54
FT /ligand="substrate"
FT BINDING 113
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 115
FT /ligand="substrate"
FT BINDING 192
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 270
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT SITE 114
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MUTAGEN 114
FT /note="S->A: Reduces the hydrolase activity."
FT /evidence="ECO:0000269|PubMed:19875455"
FT HELIX 9..12
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 13..31
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 51..54
FT /evidence="ECO:0007829|PDB:2WUE"
FT TURN 55..58
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 59..62
FT /evidence="ECO:0007829|PDB:2WUE"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 88..103
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 115..126
FT /evidence="ECO:0007829|PDB:2WUE"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 131..138
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 153..163
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 167..175
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 186..196
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 199..212
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 217..220
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 233..238
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 246..249
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 250..255
FT /evidence="ECO:0007829|PDB:2WUE"
FT STRAND 259..266
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:2WUE"
FT HELIX 276..286
FT /evidence="ECO:0007829|PDB:2WUE"
SQ SEQUENCE 291 AA; 31875 MW; FF706824615601F2 CRC64;
MTATEELTFE STSRFAEVDV DGPLKLHYHE AGVGNDQTVV LLHGGGPGAA SWTNFSRNIA
VLARHFHVLA VDQPGYGHSD KRAEHGQFNR YAAMALKGLF DQLGLGRVPL VGNSLGGGTA
VRFALDYPAR AGRLVLMGPG GLSINLFAPD PTEGVKRLSK FSVAPTRENL EAFLRVMVYD
KNLITPELVD QRFALASTPE SLTATRAMGK SFAGADFEAG MMWREVYRLR QPVLLIWGRE
DRVNPLDGAL VALKTIPRAQ LHVFGQCGHW VQVEKFDEFN KLTIEFLGGG R
