X-ray structures of small ligand-FKBP complexes provide an estimate for hydrophobic interaction energies.

P Taylor, M D Walkinshaw, P Burkhard

Journal: Journal of molecular biology 2000;295(4):953-62

PMID: 10656803

Full Text on Elsevier Science View on PubMed

Abstract

A new crystal form of native FK506 binding protein (FKBP) has been obtained which has proved useful in ligand binding studies. Three different small molecule ligand complexes and the native enzyme have been determined at higher resolution than 2.0 A. Dissociation constants of the related small molecule ligands vary from 20 mM for dimethylsulphoxide to 200 microM for tetrahydrothiophene 1-oxide. Comparison of the four available crystal structures shows that the protein structures are identical to within experimental error, but there are differences in the water structure in the active site. Analysis of the calculated buried surface areas of these related ligands provides an estimated van der Waals contribution to the binding energy of -0.5 kJ/A(2) for non-polar interactions between ligand and protein.

Address: Department of Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, Basel, CH, 4056, Switzerland.

DOI: 10.1006/jmbi.1999.3411

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MeSH Terms: Amino Acid Sequence, Binding Sites, Butanones, Crystallography, X-Ray, Dimethyl Sulfoxide, Immunophilins, Ligands, Models, Molecular, Molecular Sequence Data, Pentanones, Protein Conformation, Protein Structure, Secondary, Tacrolimus Binding Proteins, Thermodynamics