4WF2

Structure of E. coli BirA G142A bound to biotinol-5'-AMP

Summary for 4WF2

• Entry DOI: 10.2210/pdb4wf2/pdb
• Descriptor: Bifunctional ligase/repressor BirA, ((2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXY-TETRAHYDROFURAN-2-YL)METHYL 5-((3AS,4S,6AR)-2-OXO-HEXAHYDRO-1H-THIENO[3,4-D]IMIDAZOL-4-YL)PENTYL HYDROGEN PHOSPHATE (3 entities in total)
• Functional Keywords: biotin protein ligase, biotin repressor, g142a mutant, complex with biotinol-5'-amp, ligase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 36754.35

Authors

Eginton, C.,Beckett, D.,Wade, H. (deposition date: 2014-09-11, release date: 2014-10-22, Last modification date: 2023-12-27)

Primary citation

Eginton, C.,Cressman, W.J.,Bachas, S.,Wade, H.,Beckett, D.
Allosteric Coupling via Distant Disorder-to-Order Transitions.
J.Mol.Biol., 427:1695-1704, 2015

PubMed Abstract: Intrinsic disorder provides a means of maximizing allosteric coupling in proteins. However, the mechanisms by which the disorder functions in allostery remain to be elucidated. Small ligand, bio-5'-AMP, binding and dimerization of the Escherichia coli biotin repressor are allosterically coupled. Folding of a disordered loop in the allosteric effector binding site is required to realize the full coupling free energy of -4.0 ± 0.3 kcal/mol observed in the wild-type protein. Alanine substitution of a glycine residue on the dimerization surface that does not directly contribute to the dimerization interface completely abolishes this coupling. In this work, the structure of this variant, solved by X-ray crystallography, reveals a monomeric corepressor-bound protein. In the structure loops, neither of which contains the alanine substitution, on both the dimerization and effector binding surfaces that are folded in the corepressor-bound wild-type protein are disordered. The structural data combined with functional measurements indicate that allosteric coupling between ligand binding and dimerization in BirA (E. coli biotin repressor/biotin protein ligase) is achieved via reciprocal communication of disorder-to-order transitions on two distant functional surfaces.

PubMed: 25746672
DOI: 10.1016/j.jmb.2015.02.021

Experimental method

X-RAY DIFFRACTION (2.31 Å)