1b27
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STRUCTURAL RESPONSE TO MUTATION AT A PROTEIN-PROTEIN INTERFACE
OverviewOverview
We have crystallised three mutants of the barnase-barstar complex in which, interactions across the interface have been deleted by simultaneous, mutation of both residues involved in the interaction. Each mutant deletes, a different type of interaction at the interface: the first complex, bnHis102-->Ala-bsTyr29-->Phe (bn, barnase; bs, barstar), deletes a van der, Waals packing interaction; the second complex, bnLys27-->Ala-bsThr42-->Ala, deletes a hydrogen bond; the third, bnLys27-->Ala-bsAsp35-->Ala, deletes a long-range charge-charge, interaction. The contribution of each of these side-chains to the, stability of the complex is known; the coupling energy between the deleted, side-chains is also known. Despite each of the double mutants being, significantly destabilised compared with the wild-type, the effects of, mutation are local. Only small movements in the main-chain surrounding the, sites of mutation and some larger movements of neighbouring side-chains, are observed in the mutant complexes. The exact response to mutation is, context-dependent and for the same mutant can vary depending upon the, environment within the crystal. In some double mutant complexes, interfacial pockets, which are accessible to bulk solvent are formed, whereas interfacial cavities which are isolated from bulk solvent, are, formed in others. In all double mutants, water molecules fill the created, pockets and cavities. These water molecules mimic the deleted side-chains, by occupying positions close to the non-carbon atoms of truncated, side-chains and re-making many hydrogen bonds made by the truncated, side-chains in the wild-type. It remains extremely difficult, however, to, correlate energetic and structural responses to mutation because of, unknown changes in entropy and entropy-enthalpy compensation.
About this StructureAbout this Structure
1B27 is a Protein complex structure of sequences from Bacillus amyloliquefaciens. This structure superseeds the now removed PDB entry 1BV0. Active as Ribonuclease T(1), with EC number 3.1.27.3 Full crystallographic information is available from OCA.
ReferenceReference
Structural response to mutation at a protein-protein interface., Vaughan CK, Buckle AM, Fersht AR, J Mol Biol. 1999 Mar 12;286(5):1487-506. PMID:10064711
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