BIRA_MYCTU
ID BIRA_MYCTU Reviewed; 266 AA.
AC I6YFP0;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Biotin--[acetyl-CoA-carboxylase] ligase {ECO:0000305};
DE EC=6.3.4.15 {ECO:0000269|PubMed:18509457, ECO:0000269|PubMed:24723382};
DE AltName: Full=Biotin--[biotin carboxyl-carrier protein] ligase {ECO:0000305};
DE AltName: Full=Biotin--protein ligase {ECO:0000303|PubMed:18509457};
DE Short=BPL {ECO:0000303|PubMed:18509457};
DE AltName: Full=Biotin-[acetyl-CoA carboxylase] synthetase {ECO:0000305};
GN Name=birA {ECO:0000303|PubMed:18509457};
GN OrderedLocusNames=Rv3279c {ECO:0000312|EMBL:CCP46098.1};
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP DOMAIN.
RX PubMed=18509457; DOI=10.1371/journal.pone.0002320;
RA Purushothaman S., Gupta G., Srivastava R., Ramu V.G., Surolia A.;
RT "Ligand specificity of group I biotin protein ligase of Mycobacterium
RT tuberculosis.";
RL PLoS ONE 3:e2320-e2320(2008).
RN [3]
RP SUBUNIT, AND CRYSTALLIZATION.
RC STRAIN=H37Rv;
RX PubMed=18540066; DOI=10.1107/s1744309108012475;
RA Gupta V., Gupta R.K., Khare G., Surolia A., Salunke D.M., Tyagi A.K.;
RT "Crystallization and preliminary X-ray diffraction analysis of biotin
RT acetyl-CoA carboxylase ligase (BirA) from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 64:524-527(2008).
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 ACTIVITY REGULATION, AND IDENTIFICATION AS A DRUG TARGET.
RX PubMed=28942842; DOI=10.1016/j.micres.2017.08.014;
RA Bond T.E.H., Sorenson A.E., Schaeffer P.M.;
RT "A green fluorescent protein-based assay for high-throughput ligand-binding
RT studies of a mycobacterial biotin protein ligase.";
RL Microbiol. Res. 205:35-39(2017).
RN [6] {ECO:0007744|PDB:3L1A, ECO:0007744|PDB:3L2Z}
RP X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS) OF DEHYDRATED AND HYDRATED ENZYME,
RP AND SUBUNIT.
RX PubMed=20169168; DOI=10.1371/journal.pone.0009222;
RA Gupta V., Gupta R.K., Khare G., Salunke D.M., Surolia A., Tyagi A.K.;
RT "Structural ordering of disordered ligand-binding loops of biotin protein
RT ligase into active conformations as a consequence of dehydration.";
RL PLoS ONE 5:e9222-e9222(2010).
RN [7] {ECO:0007744|PDB:3RUX}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 2-266 IN COMPLEX WITH BISUBSTRATE
RP INHIBITOR BIO-AMS, AND IDENTIFICATION AS A DRUG TARGET.
RX PubMed=22118677; DOI=10.1016/j.chembiol.2011.08.013;
RA Duckworth B.P., Geders T.W., Tiwari D., Boshoff H.I., Sibbald P.A.,
RA Barry C.E., Schnappinger D., Finzel B.C., Aldrich C.C.;
RT "Bisubstrate adenylation inhibitors of biotin protein ligase from
RT Mycobacterium tuberculosis.";
RL Chem. Biol. 18:1432-1441(2011).
RN [8] {ECO:0007744|PDB:2CGH, ECO:0007744|PDB:4OP0}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 3-266 OF APOENZYME AND IN COMPLEX
RP WITH REACTION INTERMEDIATE BIOTINYL-5-AMP, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND MUTAGENESIS OF LYS-138.
RX PubMed=24723382; DOI=10.1002/pro.2475;
RA Ma Q., Akhter Y., Wilmanns M., Ehebauer M.T.;
RT "Active site conformational changes upon reaction intermediate biotinyl-5'-
RT AMP binding in biotin protein ligase from Mycobacterium tuberculosis.";
RL Protein Sci. 23:932-939(2014).
RN [9] {ECO:0007744|PDB:4XTV, ECO:0007744|PDB:4XTW, ECO:0007744|PDB:4XTX, ECO:0007744|PDB:4XTY, ECO:0007744|PDB:4XTZ, ECO:0007744|PDB:4XU0, ECO:0007744|PDB:4XU1, ECO:0007744|PDB:4XU2, ECO:0007744|PDB:4XU3}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 2-266 IN COMPLEXES WITH
RP INHIBITORS, AND IDENTIFICATION AS A DRUG TARGET.
RX PubMed=26299766; DOI=10.1021/acs.jmedchem.5b00719;
RA Bockman M.R., Kalinda A.S., Petrelli R., De la Mora-Rey T., Tiwari D.,
RA Liu F., Dawadi S., Nandakumar M., Rhee K.Y., Schnappinger D., Finzel B.C.,
RA Aldrich C.C.;
RT "Targeting Mycobacterium tuberculosis biotin protein ligase (MtBPL) with
RT nucleoside-based bisubstrate adenylation inhibitors.";
RL J. Med. Chem. 58:7349-7369(2015).
RN [10] {ECO:0007744|PDB:4XTU}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 2-266 IN COMPLEX WITH INHIBITOR.
RA Bockman M.R., Kalinda A.S., Petrelli R., De la Mora-Rey T., Tawari D.,
RA Liu F., Schnappinger D., Finzel B.C., Aldrich C.C.;
RT "Mycobacterium tuberculosis biotin ligase complexed with bisubstrate
RT inhibitor (N-({[(1R,2S,3R,4R)-4-(6-amino-9H-purin-9-yl)-2,3-
RT dihydroxycyclopentyl]methyl}sulfamoyl)-5-[(3aS,4S,6aR)-2-oxohexahydro-1H-
RT thieno[3,4-d]imidazol-4-yl]pentanamide).";
RL Submitted (JAN-2015) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the transfer of biotin onto a conserved lysine
CC residue of the biotin carboxyl carrier protein (BCCP) domain of acetyl-
CC CoA carboxylase and converts it to active holo-BCCP (PubMed:18509457,
CC PubMed:24723382). Forms an acyl-adenylate intermediate
CC (PubMed:18509457, PubMed:24723382). Cannot use GTP or desthiobiotin
CC (PubMed:18509457). {ECO:0000269|PubMed:18509457,
CC ECO:0000269|PubMed:24723382}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + biotin + L-lysyl-[protein] = AMP + diphosphate + H(+) +
CC N(6)-biotinyl-L-lysyl-[protein]; Xref=Rhea:RHEA:11756, Rhea:RHEA-
CC COMP:9752, Rhea:RHEA-COMP:10505, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57586, ChEBI:CHEBI:83144, ChEBI:CHEBI:456215;
CC EC=6.3.4.15; Evidence={ECO:0000269|PubMed:18509457,
CC ECO:0000269|PubMed:24723382};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11757;
CC Evidence={ECO:0000269|PubMed:18509457, ECO:0000269|PubMed:24723382};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + biotin + H(+) = biotinyl-5'-AMP + diphosphate;
CC Xref=Rhea:RHEA:31115, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57586, ChEBI:CHEBI:62414;
CC Evidence={ECO:0000269|PubMed:18509457, ECO:0000269|PubMed:24723382};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31116;
CC Evidence={ECO:0000269|PubMed:18509457, ECO:0000269|PubMed:24723382};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=biotinyl-5'-AMP + L-lysyl-[protein] = AMP + 2 H(+) + N(6)-
CC biotinyl-L-lysyl-[protein]; Xref=Rhea:RHEA:59732, Rhea:RHEA-
CC COMP:9752, Rhea:RHEA-COMP:10505, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:62414, ChEBI:CHEBI:83144,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:18509457,
CC ECO:0000269|PubMed:24723382};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59733;
CC Evidence={ECO:0000269|PubMed:18509457, ECO:0000269|PubMed:24723382};
CC -!- ACTIVITY REGULATION: Binding of biotin and ATP significantly increases
CC the thermal stability of BirA and leads to the formation of a high
CC affinity holoenzyme complex. {ECO:0000269|PubMed:28942842}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.420 uM for biotin {ECO:0000269|PubMed:18509457};
CC KM=21.08 uM for Mg/ATP {ECO:0000269|PubMed:18509457};
CC KM=0.20 mM for ATP {ECO:0000269|PubMed:24723382};
CC KM=5.2 uM for apo-BCCP {ECO:0000269|PubMed:18509457};
CC Note=kcat is 0.034 sec(-1) with biotin as substrate. kcat is 0.0282
CC sec(-1) with Mg/ATP as substrate. kcat is 0.030 sec(-1) with apo-BCCP
CC as substrate (PubMed:18509457). kcat is 0.017 sec(-1) with ATP as
CC substrate (PubMed:24723382). {ECO:0000269|PubMed:18509457,
CC ECO:0000269|PubMed:24723382};
CC pH dependence:
CC Optimum pH is 7.5-8.0. {ECO:0000269|PubMed:18509457};
CC -!- SUBUNIT: Monomer in solution (PubMed:18509457, PubMed:20169168,
CC PubMed:24723382). Forms dimers under specific crystallization
CC conditions (PubMed:18540066, PubMed:20169168).
CC {ECO:0000269|PubMed:18509457, ECO:0000269|PubMed:18540066,
CC ECO:0000269|PubMed:20169168, ECO:0000269|PubMed:24723382}.
CC -!- DOMAIN: Belongs to monofunctional group I BPL as it lacks the N-
CC terminal helix-turn-helix (HTH) DNA-binding domain.
CC {ECO:0000305|PubMed:18509457}.
CC -!- MISCELLANEOUS: Identified as a drug target (PubMed:22118677,
CC PubMed:26299766, PubMed:28942842). Inhibited by Bio-AMS, an
CC acylsulfamide bisubstrate inhibitor, and analogs (PubMed:22118677,
CC PubMed:26299766). Bio-AMS displays potent subnanomolar enzyme
CC inhibition and antitubercular activity against multidrug resistant and
CC extensively drug resistant Mtb strains (PubMed:22118677).
CC {ECO:0000269|PubMed:22118677, ECO:0000269|PubMed:26299766,
CC ECO:0000269|PubMed:28942842}.
CC -!- SIMILARITY: Belongs to the biotin--protein ligase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46098.1; -; Genomic_DNA.
DR RefSeq; NP_217796.1; NC_000962.3.
DR RefSeq; WP_003899999.1; NZ_NVQJ01000003.1.
DR PDB; 2CGH; X-ray; 1.80 A; A/B=1-266.
DR PDB; 3L1A; X-ray; 2.69 A; A/B=1-266.
DR PDB; 3L2Z; X-ray; 2.80 A; A/B=1-266.
DR PDB; 3RUX; X-ray; 1.70 A; A/B=2-266.
DR PDB; 4OP0; X-ray; 1.70 A; A/B=3-266.
DR PDB; 4XTU; X-ray; 1.65 A; A/B=2-266.
DR PDB; 4XTV; X-ray; 1.45 A; A/B=2-266.
DR PDB; 4XTW; X-ray; 2.30 A; A/B=2-266.
DR PDB; 4XTX; X-ray; 2.30 A; A/B=2-266.
DR PDB; 4XTY; X-ray; 1.80 A; A/B=2-266.
DR PDB; 4XTZ; X-ray; 1.90 A; A/B=2-266.
DR PDB; 4XU0; X-ray; 1.60 A; A/B=2-266.
DR PDB; 4XU1; X-ray; 1.70 A; A/B=2-266.
DR PDB; 4XU2; X-ray; 1.85 A; A/B=2-266.
DR PDB; 4XU3; X-ray; 2.24 A; A/B=2-266.
DR PDBsum; 2CGH; -.
DR PDBsum; 3L1A; -.
DR PDBsum; 3L2Z; -.
DR PDBsum; 3RUX; -.
DR PDBsum; 4OP0; -.
DR PDBsum; 4XTU; -.
DR PDBsum; 4XTV; -.
DR PDBsum; 4XTW; -.
DR PDBsum; 4XTX; -.
DR PDBsum; 4XTY; -.
DR PDBsum; 4XTZ; -.
DR PDBsum; 4XU0; -.
DR PDBsum; 4XU1; -.
DR PDBsum; 4XU2; -.
DR PDBsum; 4XU3; -.
DR AlphaFoldDB; I6YFP0; -.
DR SMR; I6YFP0; -.
DR STRING; 83332.Rv3279c; -.
DR ChEMBL; CHEMBL3611962; -.
DR PaxDb; I6YFP0; -.
DR PRIDE; I6YFP0; -.
DR DNASU; 888726; -.
DR GeneID; 888726; -.
DR KEGG; mtu:Rv3279c; -.
DR PATRIC; fig|83332.111.peg.3661; -.
DR TubercuList; Rv3279c; -.
DR eggNOG; COG0340; Bacteria.
DR OMA; AVWKHIE; -.
DR PhylomeDB; I6YFP0; -.
DR BRENDA; 6.3.4.15; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009374; F:biotin binding; IDA:CAFA.
DR GO; GO:0004077; F:biotin-[acetyl-CoA-carboxylase] ligase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:CAFA.
DR CDD; cd16442; BPL; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004408; Biotin_CoA_COase_ligase.
DR InterPro; IPR003142; BPL_C.
DR InterPro; IPR004143; BPL_LPL_catalytic.
DR Pfam; PF02237; BPL_C; 1.
DR Pfam; PF03099; BPL_LplA_LipB; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00121; birA_ligase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Biotin; Ligase; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..266
FT /note="Biotin--[acetyl-CoA-carboxylase] ligase"
FT /id="PRO_0000452501"
FT DOMAIN 14..202
FT /note="BPL/LPL catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01067"
FT BINDING 38..39
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT /evidence="ECO:0000305|PubMed:24723382"
FT BINDING 63
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT /evidence="ECO:0000305|PubMed:24723382"
FT BINDING 67
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT /evidence="ECO:0000305|PubMed:24723382"
FT BINDING 138
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT /evidence="ECO:0000305|PubMed:24723382"
FT MUTAGEN 138
FT /note="K->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:24723382"
FT HELIX 3..7
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 13..20
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 29..37
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 39..48
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 56..67
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 80..89
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 95..98
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 99..113
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:4XTX"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:4XTV"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 137..147
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 150..160
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 183..202
FT /evidence="ECO:0007829|PDB:4XTV"
FT HELIX 206..214
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 221..226
FT /evidence="ECO:0007829|PDB:4XTV"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:4OP0"
FT STRAND 232..240
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 253..259
FT /evidence="ECO:0007829|PDB:4XTV"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:4XTV"
SQ SEQUENCE 266 AA; 28121 MW; 3DE5CE48830F070F CRC64;
MTDRDRLRPP LDERSLRDQL IGAGSGWRQL DVVAQTGSTN ADLLARAASG ADIDGVVLIA
EHQTAGRGRH GRGWAATARA QIILSVGVRV VDVPVQAWGW LSLAAGLAVL DSVAPLIAVP
PAETGLKWPN DVLARGGKLA GILAEVAQPF VVLGVGLNVT QAPEEVDPDA TSLLDLGVAA
PDRNRIASRL LRELEARIIQ WRNANPQLAA DYRARSLTIG SRVRVELPGG QDVVGIARDI
DDQGRLCLDV GGRTVVVSAG DVVHLR
