DB code: T00113

CATH domain 1.10.10.10 : Arc Repressor Mutant, subunit A
3.30.930.10 : BirA Bifunctional Protein; domain 2 Catalytic domain
2.30.30.100 : SH3 type barrels.
E.C. 6.3.4.15
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.10.10 : Arc Repressor Mutant, subunit A D00510 D00452 D00077 D00517 T00055
3.30.930.10 : BirA Bifunctional Protein; domain 2 S00413 D00291 D00293 D00294 D00295 M00049

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Includes RefSeq Pfam
P06709 Bifunctional protein birA
None Biotin operon repressor
Biotin--{acetyl-CoA-carboxylase} synthetase
EC 6.3.4.15
Biotin--protein ligase
NP_418404.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_491483.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF02237 (BPL_C)
PF03099 (BPL_LplA_LipB)
PF08279 (HTH_11)
[Graphical View]

KEGG enzyme name
biotin---[acetyl-CoA-carboxylase] ligase
biotin-[acetyl-CoA carboxylase] synthetase
biotin-[acetyl coenzyme A carboxylase] synthetase
acetyl coenzyme A holocarboxylase synthetase
acetyl CoA holocarboxylase synthetase
biotin:apocarboxylase ligase
Biotin holoenzyme synthetase
HCS

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P06709 BIRA_ECOLI ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [acetyl-CoA:carbon- dioxide ligase (ADP-forming)]. Monomer.

KEGG Pathways
Map code Pathways E.C.
MAP00780 Biotin metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00120 C04735 C02188 C00020 C00013 C04681 C06250 C05921
E.C.
Compound Magnesium ATP Biotin Apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] Protein lysine AMP Pyrophosphate [Acetyl-CoA:carbon-dioxide ligase (ADP-forming)] Holo-[carboxylase] Biotinyl-5'-AMP
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amide group,amine group,fatty acid,sulfide group peptide/protein amine group,lipid,peptide/protein amine group,nucleotide phosphate group/phosphate ion peptide/protein amide group,lipid,peptide/protein,sulfide group
ChEBI 18420
 18420
 		15422
 15422
 		15956
 15956
 		16027
 16027
 		29888
 29888
PubChem 888
 888
 		5957
 5957
 		171548
 171548
 		6083
 6083
 		1023
 21961011
 1023
 21961011
1biaA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bibA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hxdA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hxdB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1biaA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bibA02 Unbound Unbound Bound:BTN Unbound Unbound Unbound Unbound Unbound Unbound
1hxdA02 Unbound Unbound Bound:BTN Unbound Unbound Unbound Unbound Unbound Unbound
1hxdB02 Unbound Unbound Bound:BTN Unbound Unbound Unbound Unbound Unbound Unbound
1biaA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bibA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hxdA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hxdB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [1] & [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1biaA01
1bibA01
1hxdA01
1hxdB01
1biaA02 ; ;LYS 183 invisible 116-124
1bibA02 ARG 118;;LYS 183 invisible 119-124
1hxdA02 ARG 118;ARG 121;LYS 183
1hxdB02 ARG 118;ARG 121;LYS 183
1biaA03
1bibA03
1hxdA03
1hxdB03

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.9259
[4]
Fig.1, p.360 2

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS)
Medline ID 93028443
PubMed ID 1409631
Journal Proc Natl Acad Sci U S A
Year 1992
Volume 89
Pages 9257-61
Authors Wilson KP, Shewchuk LM, Brennan RG, Otsuka AJ, Matthews BW
Title Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains.
Related PDB 1bia 1bib
Related UniProtKB P06709
[2]
Resource
Comments
Medline ID
PubMed ID 9750231
Journal Methods Enzymol
Year 1998
Volume 295
Pages 424-50
Authors Beckett D
Title Energetic methods to study bifunctional biotin operon repressor.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9880519
Journal J Biol Chem
Year 1999
Volume 274
Pages 1449-57
Authors Chapman-Smith A, Morris TW, Wallace JC, Cronan JE Jr
Title Molecular recognition in a post-translational modification of exceptional specificity. Mutants of the biotinylated domain of acetyl-CoA carboxylase defective in recognition by biotin protein ligase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 10470036
Journal Trends Biochem Sci
Year 1999
Volume 24
Pages 359-63
Authors Chapman-Smith A, Cronan JE Jr
Title The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10981714
Journal FEBS Lett
Year 2000
Volume 479
Pages 93-8
Authors Reche PA, Howard MJ, Broadhurst RW, Perham RN
Title Heteronuclear NMR studies of the specificity of the post-translational modification of biotinyl domains by biotinyl protein ligase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11353844
Journal Proc Natl Acad Sci U S A
Year 2001
Volume 98
Pages 6045-50
Authors Weaver LH, Kwon K, Beckett D, Matthews BW
Title Corepressor-induced organization and assembly of the biotin repressor: a model for allosteric activation of a transcriptional regulator.
Related PDB 1hxd
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11714929
Journal Protein Sci
Year 2001
Volume 10
Pages 2608-17
Authors Chapman-Smith A, Mulhern TD, Whelan F, Cronan JE Jr, Wallace JC
Title The C-terminal domain of biotin protein ligase from E. coli is required for catalytic activity.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11714930
Journal Protein Sci
Year 2001
Volume 10
Pages 2618-22
Authors Weaver LH, Kwon K, Beckett D, Matthews BW
Title Competing protein:protein interactions are proposed to control the biological switch of the E coli biotin repressor.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15033356
Journal J Mol Biol
Year 2004
Volume 337
Pages 857-69
Authors Brown PH, Cronan JE, Grotli M, Beckett D
Title The biotin repressor: modulation of allostery by corepressor analogs.
Related PDB
Related UniProtKB

Comments
This protein is bifunctional, acting both as a biotin-transferring enzyme and as a transcriptional regulator (see [1]).
As the biotin-transferring enzyme, this protein catalyzes two successive reactions. The first reaction is transfer of adenylate from ATP to the carboxylate of biotin, which results in the formation of biotinyl-5'-AMP, releasing pyrophosphate. The second reaction is transfer of the biotin moiety from the intermediate, biotinyl-5'-AMP, to the correct lysine residue of protein substrate, acetyl-CoA carboxylase.
However, the detailed mechanism of catalysis has not been elucidated.

Created Updated
2004-08-01 2009-02-26