FAD3_MYCTU
ID FAD3_MYCTU Reviewed; 507 AA.
AC P96843; F2GJQ7; I6XHJ7;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoyl:CoA ligase {ECO:0000303|PubMed:23146019};
DE Short=HIP:CoA ligase {ECO:0000303|PubMed:23146019};
DE EC=6.2.1.41 {ECO:0000269|PubMed:23146019};
GN Name=fadD3 {ECO:0000303|PubMed:23146019};
GN OrderedLocusNames=Rv3561 {ECO:0000312|EMBL:CCP46383.1};
GN ORFNames=P425_03703 {ECO:0000312|EMBL:KBJ24629.1},
GN RVBD_3561 {ECO:0000312|EMBL:AFN51579.1};
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 SEQUENCE REVISION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12368430; DOI=10.1099/00221287-148-10-2967;
RA Camus J.-C., Pryor M.J., Medigue C., Cole S.T.;
RT "Re-annotation of the genome sequence of Mycobacterium tuberculosis
RT H37Rv.";
RL Microbiology 148:2967-2973(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genome Sequencing Platform;
RA Galagan J., Kreiswirth B., Dobos K., Fortune S., Fitzgerald M., Young S.K.,
RA Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Berlin A.M., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Gnerre S., Griggs A., Gujja S., Hansen M.,
RA Howarth C., Imamovic A., Larimer J., McCowan C., Murphy C., Pearson M.,
RA Poon T., Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J.,
RA Nusbaum C., Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A.M., Kreiswirth B., Gomez J., Victor T., Desjardins C., Abeel T.,
RA Young S., Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Griggs A., Gujja S., Hansen M., Howarth C.,
RA Imamovic A., Larimer J., Murphy C., Naylor J., Pearson M., Poon T.W.,
RA Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J., Nusbaum C.,
RA Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=23146019; DOI=10.1111/mmi.12095;
RA Casabon I., Crowe A.M., Liu J., Eltis L.D.;
RT "FadD3 is an acyl-CoA synthetase that initiates catabolism of cholesterol
RT rings C and D in actinobacteria.";
RL Mol. Microbiol. 87:269-283(2013).
CC -!- FUNCTION: Involved in the catabolism of the rings C and D of
CC cholesterol. Catalyzes the ATP-dependent CoA thioesterification of
CC 3aalpha-H-4alpha(3'-propanoate)-7abeta-methylhexahydro-1,5-indanedione
CC (HIP) to yield HIP-CoA. It can also use the hydroxylated analogs of
CC HIP, 5alpha-OH HIP and 1beta-OH HIP. It requires that the side chain at
CC C17 is completely removed. {ECO:0000269|PubMed:23146019}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-
CC yl]propanoate + ATP + CoA = 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-
CC octahydro-1H-inden-4-yl]propanoyl-CoA + AMP + diphosphate;
CC Xref=Rhea:RHEA:41640, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:63692, ChEBI:CHEBI:78357,
CC ChEBI:CHEBI:456215; EC=6.2.1.41;
CC Evidence={ECO:0000269|PubMed:23146019};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41641;
CC Evidence={ECO:0000269|PubMed:23146019};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-hydroxy-3-[(3aS,4S,5R,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-
CC inden-4-yl]propanoate + ATP + CoA = 3-[(3aS,4S,5R,7aS)-5-hydroxy-7a-
CC methyl-1-oxo-octahydro-1H-inden-4-yl]propanoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:43832, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:83736,
CC ChEBI:CHEBI:83738, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:23146019};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43833;
CC Evidence={ECO:0000269|PubMed:23146019};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.8 uM for HIP (at pH 7.3 and 22 degrees Celsius)
CC {ECO:0000269|PubMed:23146019};
CC KM=3000 uM for 5alpha-OH HIP (at pH 7.3 and 22 degrees Celsius)
CC {ECO:0000269|PubMed:23146019};
CC KM=110 uM for CoASH (at pH 7.3 and 22 degrees Celsius)
CC {ECO:0000269|PubMed:23146019};
CC Note=kcat is 7.1 sec(-1) for ligase activity with HIP. kcat is 7.5
CC sec(-1) for ligase activity with CoASH (at pH 7.3 and 22 degrees
CC Celsius). kcat is 13 sec(-1) for ligase activity with 5alpha-OH HIP
CC (at pH 7.3 and 22 degrees Celsius). {ECO:0000269|PubMed:23146019};
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46383.1; -; Genomic_DNA.
DR EMBL; CP003248; AFN51579.1; -; Genomic_DNA.
DR EMBL; JLDD01000048; KBJ24629.1; -; Genomic_DNA.
DR RefSeq; NP_218078.1; NC_000962.3.
DR RefSeq; WP_003900098.1; NZ_NVQJ01000014.1.
DR AlphaFoldDB; P96843; -.
DR SMR; P96843; -.
DR STRING; 83332.Rv3561; -.
DR SwissLipids; SLP:000000991; -.
DR PaxDb; P96843; -.
DR DNASU; 887244; -.
DR GeneID; 887244; -.
DR KEGG; mtu:Rv3561; -.
DR KEGG; mtv:RVBD_3561; -.
DR TubercuList; Rv3561; -.
DR eggNOG; COG0318; Bacteria.
DR InParanoid; P96843; -.
DR OMA; YIMPKFD; -.
DR PhylomeDB; P96843; -.
DR BioCyc; MetaCyc:G185E-7838-MON; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016405; F:CoA-ligase activity; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cholesterol metabolism; Ligase; Lipid metabolism;
KW Nucleotide-binding; Reference proteome; Steroid metabolism;
KW Sterol metabolism.
FT CHAIN 1..507
FT /note="3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-
FT inden-4-yl]propanoyl:CoA ligase"
FT /id="PRO_0000430639"
FT BINDING 177..185
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 391
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 497
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 507 AA; 54095 MW; BD22EBB8EDC76C77 CRC64;
MINDLRTVPA ALDRLVRQLP DHTALIAEDR RFTSTELRDA VYGAAAALIA LGVEPADRVA
IWSPNTWHWV VACLAIHHAG AAVVPLNTRY TATEATDILD RAGAPVLFAA GLFLGADRAA
GLDRAALPAL RHVVRVPVEA DDGTWDEFIA TGAGALDAVA ARAAAVAPQD VSDILFTSGT
TGRSKGVLCA HRQSLSASAS WAANGKITSD DRYLCINPFF HNFGYKAGIL ACLQTGATLI
PHVTFDPLHA LRAIERHRIT VLPGPPTIYQ SLLDHPARKD FDLSSLRFAV TGAATVPVVL
VERMQSELDI DIVLTAYGLT EANGMGTMCR PEDDAVTVAT TCGRPFADFE LRIADDGEVL
LRGPNVMVGY LDDTEATAAA IDADGWLHTG DIGAVDQAGN LRITDRLKDM YICGGFNVYP
AEVEQVLARM DGVADAAVIG VPDQRLGEVG RAFVVARPGT GLDEASVIAY TREHLANFKT
PRSVRFVDVL PRNAAGKVSK PQLRELG
