2ewn
Ecoli Biotin Repressor with co-repressor analog
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OverviewOverview
BirA catalyzes the adenylation and subsequent covalent attachment of, biotin to the biotin carboxyl carrier protein (BCCP). In the absence of, apo-BCCP, biotin-5'-AMP acts as a co-repressor that induces BirA, dimerization and binding to the bio operator to repress biotin, biosynthesis. The crystal structures of apo-BirA, and BirA in complex with, biotin have been reported. We here describe the 2.8A resolution crystal, structure of BirA in complex with the co-repressor analog biotinol-5'-AMP., It was previously shown that the structure of apo-BirA is monomeric and, that binding of biotin weakly induces a dimeric structure in which three, disordered surface loops become organized to form the dimer interface. The, structure of the co-repressor complex is also a dimer, clearly related to, the BirA.biotin structure, but with several significant conformational, changes. A hitherto disordered "adenylate binding loop" forms a, well-defined structure covering the co-repressor. The co-repressor, buttresses the dimer interface, resulting in improved packing and a 12, degrees change in the hinge-bending angle along the dimer interface, relative to the BirA.biotin structure. This helps explain why the binding, of the co-repressor is necessary to optimize the binding of BirA to the, bioO operator. The structure reveals an unexpected use of the, nucleotide-binding motif GXGXXG in binding adenylate and controlling the, repressor function. Finally, based on structural analysis we propose that, the class of adenylating enzymes represented by BirA, lipoate protein, ligase and class II tRNA synthetases diverged early and were selected, based on their ability to sequester co-factors or amino acid residues, and, adenylation activity arose independently through functional convergence.
About this StructureAbout this Structure
2EWN is a Single protein structure of sequence from Escherichia coli with BTX as ligand. Active as [acetyl-CoA-carboxylase_ligase Biotin--[acetyl-CoA-carboxylase] ligase], with EC number 6.3.4.15 Full crystallographic information is available from OCA.
ReferenceReference
Co-repressor induced order and biotin repressor dimerization: a case for divergent followed by convergent evolution., Wood ZA, Weaver LH, Brown PH, Beckett D, Matthews BW, J Mol Biol. 2006 Mar 24;357(2):509-23. Epub 2006 Jan 6. PMID:16438984 [[Category: Biotin--[acetyl-CoA-carboxylase] ligase]]
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