Protein Engineering vol. 6 no. 1 pp. 29-35, 1993
© 1993 Oxford University Press
RESEARCH-ARTICLE |
The prediction and characterization of metal binding sites in proteins
1Laboratory of Molecular Biophysics Rex Richards Building, South Parks Road, Oxford OX1 3QU, UK 2Department of Biochemistry, University of Bath Claverton Down, Bath BA2 7AY, UK 3Present address: SciTech Software, 23 Stag Leys, Ashtead, Surrey KT21 2TD, UK 4Present address: Amgen Inc., 1840 Dehavilland Drive, Thousand Oaks, CA 91320, USA
5To whom correspondence should be addressed
The rational engineering of novel functions into proteins can only be attempted when the underlying structural scaffold on which the new function is displayed and the structure of the target protein are both well understood. To introduce functions mediated by metals it is therefore necessary to identify the principal liganding residues for the chosen metal, the required architecture of the metal-ligand complex and sites within the target protein that could accommodate such sites. Here we present a method that applies structural information from the protein data bank to the ab initio design and characterization of novel metal binding sites. The prediction method has been tested on 28 metalloprotein structures from the Brookhaven Protein Data Bank. It successfully identified >90% of the metal binding sites. In addition, we have used the method to design and characterize zinc binding sites in two antibody structures. Metal binding studies on one of these putative metalloantibodies showed metal binding, confirming the predictive power of the method.
Keywords: hydrophobicity contrast/metal binding/protein engineering/transition metal/zinc binding sites
Received April 29, 1992; revised August 24, 1992; accepted September 18, 1992.
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