ACCD6_MYCTU
ID ACCD6_MYCTU Reviewed; 473 AA.
AC P9WQH5; L0TBQ7; P63407; Q10506;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Biotin-dependent acetyl-/propionyl-coenzyme A carboxylase beta6 subunit {ECO:0000305};
DE AltName: Full=Acetyl-CoA carboxylase {ECO:0000305};
DE Short=ACC {ECO:0000303|PubMed:17114269};
DE EC=2.1.3.15 {ECO:0000269|PubMed:17114269};
DE AltName: Full=Propionyl-CoA carboxylase {ECO:0000305};
DE Short=PCC {ECO:0000303|PubMed:17114269};
DE EC=2.1.3.- {ECO:0000269|PubMed:17114269};
GN Name=accD6 {ECO:0000303|PubMed:17114269}; OrderedLocusNames=Rv2247;
GN ORFNames=MTCY427.28;
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 FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, SUBUNIT, AND INDUCTION.
RC STRAIN=H37Rv;
RX PubMed=17114269; DOI=10.1128/jb.01019-06;
RA Daniel J., Oh T.J., Lee C.M., Kolattukudy P.E.;
RT "AccD6, a member of the Fas II locus, is a functional carboxyltransferase
RT subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis.";
RL J. Bacteriol. 189:911-917(2007).
RN [3]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=21984794; DOI=10.1128/jb.05638-11;
RA Pawelczyk J., Brzostek A., Kremer L., Dziadek B., Rumijowska-Galewicz A.,
RA Fiolka M., Dziadek J.;
RT "AccD6, a key carboxyltransferase essential for mycolic acid synthesis in
RT Mycobacterium tuberculosis, is dispensable in a nonpathogenic strain.";
RL J. Bacteriol. 193:6960-6972(2011).
RN [5]
RP CRYSTALLIZATION.
RX PubMed=22139186; DOI=10.1107/s1744309111038413;
RA Niu C., Yin J., Cherney M.M., James M.N.;
RT "Expression, purification and preliminary crystallographic analysis of
RT Rv2247, the beta subunit of acyl-CoA carboxylase (ACCD6) from Mycobacterium
RT tuberculosis.";
RL Acta Crystallogr. F 67:1637-1640(2011).
RN [6] {ECO:0007744|PDB:4L6W}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
RA Anandhakrishnan M., Ehebauer M.T., Wilmanns M.;
RT "Structural analysis of the carboxyltransferase subunit of Mycobacterium
RT tuberculosis acetyl-CoA carboxylase.";
RL Submitted (JUN-2013) to the PDB data bank.
RN [7] {ECO:0007744|PDB:4FB8, ECO:0007744|PDB:4G2R}
RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF APO FORM AND IN COMPLEX WITH
RP INHIBITOR HALOXYFOP-R, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=H37Rv;
RX PubMed=25092705; DOI=10.1128/aac.02574-13;
RA Reddy M.C., Breda A., Bruning J.B., Sherekar M., Valluru S., Thurman C.,
RA Ehrenfeld H., Sacchettini J.C.;
RT "Structure, activity, and inhibition of the carboxyltransferase beta-
RT subunit of acetyl coenzyme A carboxylase (AccD6) from Mycobacterium
RT tuberculosis.";
RL Antimicrob. Agents Chemother. 58:6122-6132(2014).
RN [8] {ECO:0007744|PDB:6P7U}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP QUIZALOFOP-P.
RA Reddy M.C.M., Sacchettini J.C.;
RT "Inhibition of Mycobacterium tuberculosis acetyl-CoA
RT carboxyltransferase(AccD6) domain of acetyl-coenzyme A carboxylase by
RT quizalofop-p.";
RL Submitted (JUN-2019) to the PDB data bank.
RN [9] {ECO:0007744|PDB:6PK2}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP QUIZALOFOP-P DERIVATIVE.
RA Reddy M.C.M., Nian Z., Sacchettini J.C.;
RT "Elucidating the inhibition and specificity of binding of herbicidal
RT aryloxyphenoxypropionates derivatives to Mycobacterium tuberculosis
RT carboxyltransferasedomain of acetyl-coenzyme A(AccD6).";
RL Submitted (JUN-2019) to the PDB data bank.
RN [10] {ECO:0007744|PDB:6PRW}
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP QUIZALOFOP-P DERIVATIVE.
RA Reddy M.C.M., Nian Z., Sacchettini J.C.;
RT "Crystal structure of the carboxyltransferase subunit of ACC (ACCD6) in
RT complex with inhibitor quizalofop-p deverivative from Mycobacterium
RT tuberculosis.";
RL Submitted (JUL-2019) to the PDB data bank.
RN [11] {ECO:0007744|PDB:6TZV}
RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP PHENYL-CYCLODIAONE.
RA Reddy M.C.M., Zhou N., Sacchettini J.;
RT "Novel herbicidal derivatives that inhibit carboxyltransferase subunit of
RT the acetyl-CoA carboxylase in Mycobacterium tuberculosis.";
RL Submitted (AUG-2019) to the PDB data bank.
CC -!- FUNCTION: Component of a biotin-dependent acyl-CoA carboxylase complex.
CC This subunit transfers the CO2 from carboxybiotin to the CoA ester
CC substrate (PubMed:17114269). When associated with the alpha3 subunit
CC AccA3, is involved in the carboxylation of acetyl-CoA and propionyl-
CC CoA, with a preference for acetyl-CoA (PubMed:17114269).
CC {ECO:0000269|PubMed:17114269}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N(6)-carboxybiotinyl-L-lysyl-[protein] = malonyl-
CC CoA + N(6)-biotinyl-L-lysyl-[protein]; Xref=Rhea:RHEA:54728,
CC Rhea:RHEA-COMP:10505, Rhea:RHEA-COMP:10506, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:83144, ChEBI:CHEBI:83145; EC=2.1.3.15;
CC Evidence={ECO:0000269|PubMed:17114269, ECO:0000269|PubMed:25092705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54729;
CC Evidence={ECO:0000269|PubMed:17114269};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-carboxybiotinyl-L-lysyl-[protein] + propanoyl-CoA =
CC methylmalonyl-CoA + N(6)-biotinyl-L-lysyl-[protein];
CC Xref=Rhea:RHEA:66612, Rhea:RHEA-COMP:10505, Rhea:RHEA-COMP:10506,
CC ChEBI:CHEBI:57392, ChEBI:CHEBI:59916, ChEBI:CHEBI:83144,
CC ChEBI:CHEBI:83145; Evidence={ECO:0000269|PubMed:17114269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66613;
CC Evidence={ECO:0000269|PubMed:17114269};
CC -!- ACTIVITY REGULATION: Activity of the AccA3/AccD6 complex is inhibited
CC by interaction with the epsilon subunit AccE5 (PubMed:17114269).
CC Inhibited by dimethyl itaconate, C75, the herbicide haloxyfop,
CC cerulenin, and 1,2-cyclohexanedione (PubMed:17114269, PubMed:25092705).
CC {ECO:0000269|PubMed:17114269, ECO:0000269|PubMed:25092705}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.9 mM for acetyl-CoA (in the presence of alpha3 subunit)
CC {ECO:0000269|PubMed:17114269};
CC KM=0.97 mM for propionyl-CoA (in the presence of alpha3 subunit)
CC {ECO:0000269|PubMed:17114269};
CC KM=0.39 mM for malonyl-CoA {ECO:0000269|PubMed:25092705};
CC Vmax=1.1 nmol/min/mg enzyme with acetyl-CoA as substrate (in the
CC presence of alpha3 subunit) {ECO:0000269|PubMed:17114269};
CC Vmax=0.36 nmol/min/mg enzyme with propionyl-CoA as substrate (in the
CC presence of alpha3 subunit) {ECO:0000269|PubMed:17114269};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000305|PubMed:17114269}.
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000269|PubMed:21984794, ECO:0000305|PubMed:17114269}.
CC -!- SUBUNIT: Homodimer (PubMed:25092705). The biotin-dependent acyl-CoA
CC carboxylase complex is composed of AccA3, which contains the biotin
CC carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains,
CC and AccD6, which contains the carboxyl transferase (CT) domain
CC (PubMed:17114269). The AccA3/AccD6 complex forms a dodecamer
CC (PubMed:17114269). {ECO:0000269|PubMed:17114269,
CC ECO:0000269|PubMed:25092705}.
CC -!- INDUCTION: Expressed at higher levels during the exponential growth
CC phase. {ECO:0000269|PubMed:17114269}.
CC -!- DISRUPTION PHENOTYPE: Essential. Cannot be deleted. Limited expression
CC level affects growth, mycolic acid content and cell morphology.
CC {ECO:0000269|PubMed:21984794}.
CC -!- MISCELLANEOUS: AccD6 is dispensable in nonpathogenic strains.
CC {ECO:0000269|PubMed:21984794}.
CC -!- SIMILARITY: Belongs to the AccD/PCCB family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45027.1; -; Genomic_DNA.
DR PIR; C70779; C70779.
DR RefSeq; NP_216763.1; NC_000962.3.
DR RefSeq; WP_003900487.1; NZ_NVQJ01000008.1.
DR PDB; 4FB8; X-ray; 3.00 A; A/B=1-473.
DR PDB; 4G2R; X-ray; 2.28 A; A/B=1-473.
DR PDB; 4L6W; X-ray; 1.95 A; A/B=1-473.
DR PDB; 6P7U; X-ray; 2.20 A; A/B/C/D=1-473.
DR PDB; 6PK2; X-ray; 2.40 A; A/B/C/D/E/F/G/H=1-473.
DR PDB; 6PRW; X-ray; 2.61 A; A/B/C/D/E/F/G/H=1-473.
DR PDB; 6TZV; X-ray; 2.39 A; A/B/C/D/E/F/G/H=1-473.
DR PDBsum; 4FB8; -.
DR PDBsum; 4G2R; -.
DR PDBsum; 4L6W; -.
DR PDBsum; 6P7U; -.
DR PDBsum; 6PK2; -.
DR PDBsum; 6PRW; -.
DR PDBsum; 6TZV; -.
DR AlphaFoldDB; P9WQH5; -.
DR SMR; P9WQH5; -.
DR STRING; 83332.Rv2247; -.
DR iPTMnet; P9WQH5; -.
DR PaxDb; P9WQH5; -.
DR DNASU; 887671; -.
DR GeneID; 45426227; -.
DR GeneID; 887671; -.
DR KEGG; mtu:Rv2247; -.
DR TubercuList; Rv2247; -.
DR eggNOG; COG4799; Bacteria.
DR OMA; AYDVHPI; -.
DR PhylomeDB; P9WQH5; -.
DR BioCyc; MetaCyc:G185E-6463-MON; -.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00915; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009317; C:acetyl-CoA carboxylase complex; IDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0003989; F:acetyl-CoA carboxylase activity; IDA:MTBBASE.
DR GO; GO:0004658; F:propionyl-CoA carboxylase activity; IBA:GO_Central.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0019367; P:fatty acid elongation, saturated fatty acid; IDA:MTBBASE.
DR InterPro; IPR034733; AcCoA_carboxyl.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR011763; COA_CT_C.
DR InterPro; IPR011762; COA_CT_N.
DR Pfam; PF01039; Carboxyl_trans; 1.
DR SUPFAM; SSF52096; SSF52096; 2.
DR PROSITE; PS50989; COA_CT_CTER; 1.
DR PROSITE; PS50980; COA_CT_NTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..473
FT /note="Biotin-dependent acetyl-/propionyl-coenzyme A
FT carboxylase beta6 subunit"
FT /id="PRO_0000199800"
FT DOMAIN 2..224
FT /note="CoA carboxyltransferase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01136"
FT DOMAIN 225..473
FT /note="CoA carboxyltransferase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01137"
FT BINDING 99
FT /ligand="(R)-haloxyfop"
FT /ligand_id="ChEBI:CHEBI:136690"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0007744|PDB:4G2R"
FT BINDING 138
FT /ligand="(R)-haloxyfop"
FT /ligand_id="ChEBI:CHEBI:136690"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0007744|PDB:4G2R"
FT BINDING 185
FT /ligand="(R)-haloxyfop"
FT /ligand_id="ChEBI:CHEBI:136690"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0007744|PDB:4G2R"
FT BINDING 334
FT /ligand="(R)-haloxyfop"
FT /ligand_id="ChEBI:CHEBI:136690"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0007744|PDB:4G2R"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:6P7U"
FT HELIX 18..25
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 39..49
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 52..59
FT /evidence="ECO:0007829|PDB:4L6W"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 70..86
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 90..96
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 104..121
FT /evidence="ECO:0007829|PDB:4L6W"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 127..136
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 141..145
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 156..160
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 162..169
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 175..179
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 181..186
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:4G2R"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 198..213
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 220..225
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 245..251
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 269..276
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:4L6W"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 297..313
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 317..323
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 335..350
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 355..364
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 365..370
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 379..383
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 388..392
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 394..398
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 403..408
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 411..428
FT /evidence="ECO:0007829|PDB:4L6W"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:6P7U"
FT HELIX 432..437
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:4L6W"
FT HELIX 450..460
FT /evidence="ECO:0007829|PDB:4L6W"
SQ SEQUENCE 473 AA; 50136 MW; 94AD7EBD88F233C3 CRC64;
MTIMAPEAVG ESLDPRDPLL RLSNFFDDGS VELLHERDRS GVLAAAGTVN GVRTIAFCTD
GTVMGGAMGV EGCTHIVNAY DTAIEDQSPI VGIWHSGGAR LAEGVRALHA VGQVFEAMIR
ASGYIPQISV VVGFAAGGAA YGPALTDVVV MAPESRVFVT GPDVVRSVTG EDVDMASLGG
PETHHKKSGV CHIVADDELD AYDRGRRLVG LFCQQGHFDR SKAEAGDTDI HALLPESSRR
AYDVRPIVTA ILDADTPFDE FQANWAPSMV VGLGRLSGRT VGVLANNPLR LGGCLNSESA
EKAARFVRLC DAFGIPLVVV VDVPGYLPGV DQEWGGVVRR GAKLLHAFGE CTVPRVTLVT
RKTYGGAYIA MNSRSLNATK VFAWPDAEVA VMGAKAAVGI LHKKKLAAAP EHEREALHDQ
LAAEHERIAG GVDSALDIGV VDEKIDPAHT RSKLTEALAQ APARRGRHKN IPL
