HSAC_MYCTU
ID HSAC_MYCTU Reviewed; 300 AA.
AC P9WNW7; L0TFW3; P96850; Q7D597;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Iron-dependent extradiol dioxygenase;
DE EC=1.13.11.25 {ECO:0000269|PubMed:17264217};
GN Name=hsaC; Synonyms=bphC; OrderedLocusNames=Rv3568c;
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 FUNCTION AS AN EXTRADIOL DIOXYGENASE, CATALYTIC ACTIVITY, AND
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 (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND IRON
RP ION, DISRUPTION PHENOTYPE, COFACTOR, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19300498; DOI=10.1371/journal.ppat.1000344;
RA Yam K.C., D'Angelo I., Kalscheuer R., Zhu H., Wang J.X., Snieckus V.,
RA Ly L.H., Converse P.J., Jacobs W.R. Jr., Strynadka N., Eltis L.D.;
RT "Studies of a ring-cleaving dioxygenase illuminate the role of cholesterol
RT metabolism in the pathogenesis of Mycobacterium tuberculosis.";
RL PLoS Pathog. 5:E1000344-E1000344(2009).
CC -!- FUNCTION: Catalyzes the meta-cleavage of 3,4-dihydroxy-9,10-
CC seconandrost-1,3,5(10)-triene-9,17-dione (3,4-DHSA) to produce 4,5-
CC 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oic acid
CC (4,9-DSHA). {ECO:0000269|PubMed:17264217}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione +
CC O2 = (1E,2Z)-3-hydroxy-5,9,17-trioxo-4,5:9,10-disecoandrosta-1(10),2-
CC dien-4-oate + H(+); Xref=Rhea:RHEA:21352, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15896, ChEBI:CHEBI:63690;
CC EC=1.13.11.25; Evidence={ECO:0000269|PubMed:17264217};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:19300498};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:19300498};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.9 uM for 3,4-DHSA (at pH 8 and at 25 degrees Celsius)
CC {ECO:0000269|PubMed:17264217};
CC KM=8.5 uM for 2,3-dihydroxybiphenyl (DHB) (at pH 8 and at 25 degrees
CC Celsius) {ECO:0000269|PubMed:17264217};
CC Vmax=12 umol/sec/mg enzyme with 3,4-DHSA as substrate (at pH 8 and at
CC 25 degrees Celsius) {ECO:0000269|PubMed:17264217};
CC Vmax=2.5 umol/sec/mg enzyme with DHB as substrate (at pH 8 and at 25
CC degrees Celsius) {ECO:0000269|PubMed:17264217};
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC -!- SUBUNIT: Homodimer, but may form a homooctamer.
CC {ECO:0000269|PubMed:19300498}.
CC -!- INDUCTION: Induced by KstR. {ECO:0000269|PubMed:17635188}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene completely fail to grow
CC on cholesterol due the blockage of the catabolic pathway and develop a
CC pink color consistent with the accumulation of toxic catechols. Mice
CC intravenously infected with the mutant survive substantially longer
CC than those infected with the wild-type. {ECO:0000269|PubMed:19300498}.
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 extradiol ring-cleavage dioxygenase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46391.1; -; Genomic_DNA.
DR PIR; F70605; F70605.
DR RefSeq; NP_218085.1; NC_000962.3.
DR RefSeq; WP_003419378.1; NZ_NVQJ01000014.1.
DR PDB; 2ZI8; X-ray; 2.20 A; A/B=1-300.
DR PDB; 2ZYQ; X-ray; 2.00 A; A/B=1-300.
DR PDBsum; 2ZI8; -.
DR PDBsum; 2ZYQ; -.
DR AlphaFoldDB; P9WNW7; -.
DR SMR; P9WNW7; -.
DR STRING; 83332.Rv3568c; -.
DR DrugBank; DB08542; 3,4-dihydroxy-9,10-secoandrosta-1(10),2,4-triene-9,17-dione.
DR SwissLipids; SLP:000001005; -.
DR PaxDb; P9WNW7; -.
DR DNASU; 887886; -.
DR GeneID; 887886; -.
DR KEGG; mtu:Rv3568c; -.
DR TubercuList; Rv3568c; -.
DR eggNOG; COG0346; Bacteria.
DR OMA; KMSATLG; -.
DR PhylomeDB; P9WNW7; -.
DR BioCyc; MetaCyc:G185E-7846-MON; -.
DR SABIO-RK; P9WNW7; -.
DR UniPathway; UPA00296; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0047071; F:3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione 4,5-dioxygenase activity; IDA:MTBBASE.
DR GO; GO:0008198; F:ferrous iron binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IDA:MTBBASE.
DR GO; GO:0019439; P:aromatic compound catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006707; P:cholesterol catabolic process; IDA:MTBBASE.
DR GO; GO:0070723; P:response to cholesterol; IEP:MTBBASE.
DR Gene3D; 3.10.180.10; -; 2.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR037523; VOC.
DR InterPro; IPR000486; Xdiol_ring_cleave_dOase_1/2.
DR Pfam; PF00903; Glyoxalase; 1.
DR SUPFAM; SSF54593; SSF54593; 2.
DR PROSITE; PS00082; EXTRADIOL_DIOXYGENAS; 1.
DR PROSITE; PS51819; VOC; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Aromatic hydrocarbons catabolism; Cholesterol metabolism;
KW Dioxygenase; Iron; Lipid degradation; Lipid metabolism; Metal-binding;
KW Oxidoreductase; Reference proteome; Repeat; Steroid metabolism;
KW Sterol metabolism.
FT CHAIN 1..300
FT /note="Iron-dependent extradiol dioxygenase"
FT /id="PRO_0000404507"
FT DOMAIN 5..120
FT /note="VOC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT DOMAIN 142..270
FT /note="VOC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 145
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 200
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19300498"
FT BINDING 215
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 215
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19300498"
FT BINDING 250
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19300498"
FT BINDING 256
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19300498"
FT BINDING 266
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT STRAND 5..14
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 40..48
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 60..67
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT HELIX 71..84
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT HELIX 93..99
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 145..149
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT HELIX 153..161
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 167..174
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:2ZI8"
FT STRAND 188..199
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 201..207
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 210..222
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT HELIX 223..235
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 240..250
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 262..269
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:2ZYQ"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:2ZI8"
SQ SEQUENCE 300 AA; 33582 MW; 2AA94528D119ACB0 CRC64;
MSIRSLGYLR IEATDMAAWR EYGLKVLGMV EGKGAPEGAL YLRMDDFPAR LVVVPGEHDR
LLEAGWECAN AEGLQEIRNR LDLEGTPYKE ATAAELADRR VDEMIRFADP SGNCLEVFHG
TALEHRRVVS PYGHRFVTGE QGMGHVVLST RDDAEALHFY RDVLGFRLRD SMRLPPQMVG
RPADGPPAWL RFFGCNPRHH SLAFLPMPTS SGIVHLMVEV EQADDVGLCL DRALRRKVPM
SATLGRHVND LMLSFYMKTP GGFDIEFGCE GRQVDDRDWI ARESTAVSLW GHDFTVGARG
