FADA6_MYCTU
ID FADA6_MYCTU Reviewed; 407 AA.
AC I6XHJ3;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Steroid 3-ketoacyl-CoA thiolase FadA6 {ECO:0000305};
DE EC=2.3.1.16 {ECO:0000269|PubMed:28377529};
DE AltName: Full=Acetyl-CoA acetyltransferase FadA6 {ECO:0000305};
GN Name=fadA6 {ECO:0000303|PubMed:28377529};
GN OrderedLocusNames=Rv3556c {ECO:0000312|EMBL:CCP46378.1};
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 PROTEIN SEQUENCE OF 32-46, AND SEQUENCE REVISION TO N-TERMINUS.
RC STRAIN=H37Rv;
RX PubMed=34915127; DOI=10.1016/j.ygeno.2021.12.001;
RA Shi J., Meng S., Wan L., Zhang Z., Jiang S., Zhu H., Dai E., Chang L.,
RA Gao H., Wan K., Zhang L., Zhao X., Liu H., Lyu Z., Zhang Y., Xu P.;
RT "Deep N-terminomics of Mycobacterium tuberculosis H37Rv extensively correct
RT annotated encoding genes.";
RL Genomics 114:292-304(2022).
RN [3]
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC STRAIN=Erdman;
RX PubMed=28377529; DOI=10.1128/mbio.00321-17;
RA Crowe A.M., Casabon I., Brown K.L., Liu J., Lian J., Rogalski J.C.,
RA Hurst T.E., Snieckus V., Foster L.J., Eltis L.D.;
RT "Catabolism of the last two steroid rings in Mycobacterium tuberculosis and
RT other bacteria.";
RL MBio 8:e00321-e00321(2017).
CC -!- FUNCTION: May be involved in the final steps of cholesterol and steroid
CC degradation (PubMed:28377529). Catalyzes the formation of 4-methyl-5-
CC oxo-octanedioyl-CoA (MOODA-CoA) and acetyl-CoA from 6-methyl-3,7-
CC dioxodecanedioyl-CoA (MeDODA-CoA) and coenzyme A (Probable).
CC {ECO:0000269|PubMed:28377529, ECO:0000305|PubMed:28377529}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + an acyl-CoA = a 3-oxoacyl-CoA + CoA;
CC Xref=Rhea:RHEA:21564, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:58342, ChEBI:CHEBI:90726; EC=2.3.1.16;
CC Evidence={ECO:0000305|PubMed:28377529};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21566;
CC Evidence={ECO:0000305|PubMed:28377529};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-methyl-3,7-dioxodecanedioyl-CoA + CoA = 4-methyl-5-oxo-
CC octanedioyl-CoA + acetyl-CoA; Xref=Rhea:RHEA:66368,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:167102,
CC ChEBI:CHEBI:167103; Evidence={ECO:0000269|PubMed:28377529};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66369;
CC Evidence={ECO:0000269|PubMed:28377529};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=300 uM for acetoacetyl-CoA {ECO:0000269|PubMed:28377529};
CC Note=kcat is 4.8 sec(-1) with acetoacetyl-CoA as substrate.
CC {ECO:0000269|PubMed:28377529};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000269|PubMed:28377529}.
CC -!- MISCELLANEOUS: Turnover of MeDODA-CoA is low and FadA6 may not be the
CC physiological thiolase responsible for MOODA-CoA formation.
CC {ECO:0000269|PubMed:28377529}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP46378.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000269|PubMed:34915127};
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DR EMBL; AL123456; CCP46378.1; ALT_INIT; Genomic_DNA.
DR RefSeq; NP_218073.1; NC_000962.3.
DR RefSeq; WP_003419328.1; NZ_NVQJ01000014.1.
DR AlphaFoldDB; I6XHJ3; -.
DR SMR; I6XHJ3; -.
DR STRING; 83332.Rv3556c; -.
DR PaxDb; I6XHJ3; -.
DR PRIDE; I6XHJ3; -.
DR DNASU; 887285; -.
DR GeneID; 887285; -.
DR KEGG; mtu:Rv3556c; -.
DR PATRIC; fig|83332.111.peg.3961; -.
DR TubercuList; Rv3556c; -.
DR eggNOG; COG0183; Bacteria.
DR OMA; MPEAYVI; -.
DR PhylomeDB; I6XHJ3; -.
DR BioCyc; MetaCyc:G185E-7833-MON; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003988; F:acetyl-CoA C-acyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006707; P:cholesterol catabolic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00751; thiolase; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR002155; Thiolase.
DR InterPro; IPR016039; Thiolase-like.
DR InterPro; IPR020617; Thiolase_C.
DR InterPro; IPR020613; Thiolase_CS.
DR InterPro; IPR020616; Thiolase_N.
DR Pfam; PF02803; Thiolase_C; 1.
DR Pfam; PF00108; Thiolase_N; 1.
DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR TIGRFAMs; TIGR01930; AcCoA-C-Actrans; 1.
DR PROSITE; PS00737; THIOLASE_2; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Cholesterol metabolism; Direct protein sequencing;
KW Lipid metabolism; Reference proteome; Steroid metabolism;
KW Sterol metabolism; Transferase.
FT CHAIN 1..407
FT /note="Steroid 3-ketoacyl-CoA thiolase FadA6"
FT /id="PRO_0000452312"
FT ACT_SITE 110
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:I6XHI4"
FT ACT_SITE 363
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:I6XHI4"
FT ACT_SITE 393
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:I6XHI4"
FT BINDING 178
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:I6XHI4"
FT BINDING 237..239
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:I6XHI4"
FT BINDING 262
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:I6XHI4"
FT BINDING 395
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:I6XHI4"
SQ SEQUENCE 407 AA; 42981 MW; 50E579E0FACF72B7 CRC64;
MPRVDDDAVG VPLTGNGRGA VMTEAYVIDA VRTAVGKRGG ALAGIHPVDL GALAWRGLLD
RTDIDPAAVD DVIAGCVDAI GGQAGNIARL SWLAAGYPEE VPGVTVDRQC GSSQQAISFG
AQAIMSGTAD VIVAGGVQNM SQIPISSAMT VGEQFGFTSP TNESKQWLHR YGDQEISQFR
GSELIAEKWN LSREEMERYS LTSHERAFAA IRAGHFENEI ITVETESGPF RVDEGPRESS
LEKMAGLQPL VEGGRLTAAM ASQISDGASA VLLASERAVK DHGLRPRARI HHISARAADP
VFMLTGPIPA TRYALDKTGL AIDDIDTVEI NEAFAPVVMA WLKEIKADPA KVNPNGGAIA
LGHPLGATGA KLFTTMLGEL ERIGGRYGLQ TMCEGGGTAN VTIIERL
