ID HSAA_MYCTU Reviewed; 394 AA.
AC P9WJA1; L0TCY6; P96852; Q7D595;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 27-MAR-2024, entry version 51.
DE RecName: Full=Flavin-dependent monooxygenase, oxygenase subunit HsaA;
DE EC=1.14.14.12 {ECO:0000269|PubMed:20448045};
DE AltName: Full=3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione 4-hydroxylase, oxygenase subunit;
DE AltName: Full=3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione monooxygenase;
GN Name=hsaA {ECO:0000303|PubMed:20448045}; OrderedLocusNames=Rv3570c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011445;
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 X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), FUNCTION AS A HYDROXYLASE, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, AND
RP SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20448045; DOI=10.1074/jbc.m109.099028;
RA Dresen C., Lin L.Y., D'Angelo I., Tocheva E.I., Strynadka N., Eltis L.D.;
RT "A flavin-dependent monooxygenase from Mycobacterium tuberculosis involved
RT in cholesterol catabolism.";
RL J. Biol. Chem. 285:22264-22275(2010).
CC -!- FUNCTION: Catalyzes the o-hydroxylation of 3-hydroxy-9,10-secoandrosta-
CC 1,3,5(10)-triene-9,17-dione (3-HSA) to 3,4-dihydroxy-9,10-secoandrosta-
CC 1,3,5(10)-triene-9,17-dione (3,4-DHSA) in the catabolism of
CC cholesterol. Can also use 3,17-dihydroxy-9,10-seconandrost-1,3,5(10)-
CC triene-9-one (3,17-DHSA), but it has higher specificity for 3-HSA than
CC for 3,17-DHSA. Can use either FADH(2) or FMNH(2) as flavin cosubstrate.
CC Also catalyzes the o-hydroxylation of a range of p-substituted phenols
CC to generate the corresponding catechols. {ECO:0000269|PubMed:20448045}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione +
CC FMNH2 + O2 = 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-
CC dione + FMN + H(+) + H2O; Xref=Rhea:RHEA:31731, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15896,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:63245;
CC EC=1.14.14.12; Evidence={ECO:0000269|PubMed:20448045};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31732;
CC Evidence={ECO:0000269|PubMed:20448045};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,17-dihydroxy-9,10-secoandrost-1,3,5(10)-triene-9-one + FMNH2
CC + O2 = 3,4,17-trihydroxy-9,10-secoandrost-1,3,5(10)-triene-9-one +
CC FMN + H(+) + H2O; Xref=Rhea:RHEA:45988, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:85575, ChEBI:CHEBI:85576;
CC Evidence={ECO:0000269|PubMed:20448045};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45989;
CC Evidence={ECO:0000269|PubMed:20448045};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=97 uM for 3-HSA (with FAD at pH 7 and at 25 degrees Celsius)
CC {ECO:0000269|PubMed:20448045};
CC KM=100 uM for oxygen (with FMN at pH 7 and at 25 degrees Celsius)
CC {ECO:0000269|PubMed:20448045};
CC KM=200 uM for 3-HSA (with FMN at pH 7 and at 25 degrees Celsius)
CC {ECO:0000269|PubMed:20448045};
CC KM=350 uM for 3,17-DHSA (with FMN at pH 7 and at 25 degrees Celsius)
CC {ECO:0000269|PubMed:20448045};
CC KM=1440 uM for 3-hydroxybiphenyl (3-HB) (with FMN at pH 7 and at 25
CC degrees Celsius) {ECO:0000269|PubMed:20448045};
CC -!- PATHWAY: Lipid metabolism; steroid biosynthesis.
CC -!- SUBUNIT: Homotetramer under anaerobic conditions. HsaAB monooxygenase
CC consists of an oxygenase component HsaA and a reductase component HsaB.
CC {ECO:0000269|PubMed:20448045}.
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 HpaH/HsaA monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46393.1; -; Genomic_DNA.
DR PIR; H70605; H70605.
DR RefSeq; NP_218087.1; NC_000962.3.
DR RefSeq; WP_003900101.1; NZ_NVQJ01000014.1.
DR PDB; 3AFE; X-ray; 2.50 A; A/B/C/D=1-394.
DR PDB; 3AFF; X-ray; 2.00 A; A/B=1-394.
DR PDBsum; 3AFE; -.
DR PDBsum; 3AFF; -.
DR AlphaFoldDB; P9WJA1; -.
DR SMR; P9WJA1; -.
DR STRING; 83332.Rv3570c; -.
DR SwissLipids; SLP:000001164; -.
DR PaxDb; 83332-Rv3570c; -.
DR GeneID; 887241; -.
DR KEGG; mtu:Rv3570c; -.
DR TubercuList; Rv3570c; -.
DR eggNOG; COG1960; Bacteria.
DR InParanoid; P9WJA1; -.
DR OrthoDB; 3404950at2; -.
DR PhylomeDB; P9WJA1; -.
DR BioCyc; MetaCyc:G185E-7848-MONOMER; -.
DR BRENDA; 1.14.14.12; 3445.
DR UniPathway; UPA00062; -.
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:0036383; F:3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; 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:0006707; P:cholesterol catabolic process; IDA:MTBBASE.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:UniProtKB.
DR CDD; cd01159; NcnH; 1.
DR Gene3D; 1.10.540.10; Acyl-CoA dehydrogenase/oxidase, N-terminal domain; 1.
DR Gene3D; 2.40.110.10; Butyryl-CoA Dehydrogenase, subunit A, domain 2; 1.
DR Gene3D; 1.20.140.10; Butyryl-CoA Dehydrogenase, subunit A, domain 3; 1.
DR InterPro; IPR013107; Acyl-CoA_DH_C.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR013786; AcylCoA_DH/ox_N.
DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom_sf.
DR PANTHER; PTHR48083:SF19; FLAVIN-DEPENDENT MONOOXYGENASE, OXYGENASE SUBUNIT HSAA; 1.
DR PANTHER; PTHR48083; MEDIUM-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, MITOCHONDRIAL-RELATED; 1.
DR Pfam; PF08028; Acyl-CoA_dh_2; 1.
DR Pfam; PF02771; Acyl-CoA_dh_N; 1.
DR PIRSF; PIRSF016578; HsaA; 1.
DR SUPFAM; SSF47203; Acyl-CoA dehydrogenase C-terminal domain-like; 1.
DR SUPFAM; SSF56645; Acyl-CoA dehydrogenase NM domain-like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aromatic hydrocarbons catabolism; FAD; Flavoprotein; FMN;
KW Lipid degradation; Lipid metabolism; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroid metabolism.
FT CHAIN 1..394
FT /note="Flavin-dependent monooxygenase, oxygenase subunit
FT HsaA"
FT /id="PRO_0000404501"
FT BINDING 84
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 118..120
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 141..143
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 263
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 346..347
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 368..369
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT HELIX 9..33
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 65..76
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 80..96
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 101..108
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 123..129
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 132..142
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 149..159
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 162..172
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:3AFE"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 193..203
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:3AFF"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 210..214
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 233..259
FT /evidence="ECO:0007829|PDB:3AFF"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:3AFE"
FT HELIX 286..309
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 316..342
FT /evidence="ECO:0007829|PDB:3AFF"
FT TURN 346..349
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 354..370
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 374..377
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 384..386
FT /evidence="ECO:0007829|PDB:3AFF"
FT HELIX 390..393
FT /evidence="ECO:0007829|PDB:3AFF"
SQ SEQUENCE 394 AA; 43143 MW; F3103435D8EB1485 CRC64;
MTSIQQRDAQ SVLAAIDNLL PEIRDRAQAT EDLRRLPDET VKALDDVGFF TLLQPQQWGG
LQCDPALFFE ATRRLASVCG STGWVSSIVG VHNWHLALFD QRAQEEVWGE DPSTRISSSY
APMGAGVVVD GGYLVNGSWN WSSGCDHASW TFVGGPVIKD GRPVDFGSFL IPRSEYEIKD
VWYVVGLRGT GSNTLVVKDV FVPRHRFLSY KAMNDHTAGG LATNSAPVYK MPWGTMHPTT
ISAPIVGMAY GAYAAHVEHQ GKRVRAAFAG EKAKDDPFAK VRIAEAASDI DAAWRQLIGN
VSDEYALLAA GKEIPFELRA RARRDQVRAT GRSIASIDRL FEASGATALS NEAPIQRFWR
DAHAGRVHAA NDPERAYVIF GNHEFGLPPG DTMV
//
