2ewn: Difference between revisions
New page: left|200px<br /><applet load="2ewn" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ewn, resolution 2.80Å" /> '''Ecoli Biotin Repress... |
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[[Image:2ewn.gif|left|200px]]<br /><applet load="2ewn" size=" | [[Image:2ewn.gif|left|200px]]<br /><applet load="2ewn" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2ewn, resolution 2.80Å" /> | caption="2ewn, resolution 2.80Å" /> | ||
'''Ecoli Biotin Repressor with co-repressor analog'''<br /> | '''Ecoli Biotin Repressor with co-repressor analog'''<br /> | ||
==Overview== | ==Overview== | ||
BirA catalyzes the adenylation and subsequent covalent attachment of | 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 Structure== | ==About this Structure== | ||
2EWN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with BTX as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Biotin--[acetyl-CoA-carboxylase]_ligase Biotin--[acetyl-CoA-carboxylase] ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.15 6.3.4.15] Full crystallographic information is available from [http:// | 2EWN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=BTX:'>BTX</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Biotin--[acetyl-CoA-carboxylase]_ligase Biotin--[acetyl-CoA-carboxylase] ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.15 6.3.4.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EWN OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Matthews, B | [[Category: Matthews, B W.]] | ||
[[Category: Weaver, L | [[Category: Weaver, L H.]] | ||
[[Category: Wood, Z | [[Category: Wood, Z A.]] | ||
[[Category: BTX]] | [[Category: BTX]] | ||
[[Category: biotin]] | [[Category: biotin]] | ||
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[[Category: helix-turn-helix]] | [[Category: helix-turn-helix]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:15:19 2008'' | ||
Revision as of 18:15, 21 February 2008
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Ecoli Biotin Repressor with co-repressor analog
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 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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