ELECTROPHILE-NUCLEOPHILE INTERACTION IN PROTEIN STRUCTURES. Pinak Chakrabarti and Debnath Pal, Division of Physical Chemistry, National Chemical Laboratory, Pune 411008, India.

Although the various nonbonded interactions in protein structures have been well identified, their use to explain protein folding, substrate recognition and catalysis has not been an unqualified success. We have been investigating the existence of other strong directional interactions in proteins. When in close proximity in small organic molecules, an electrophile and a nucleophile have been found to orient themselves in a very specific way so as to affect the overall conformation of the molecule.¹ Our analysis of proteins structures, as stored in the Brookhaven Protein Data Bank, has identified a similar interaction where a thiolate anion (S) (metal-bound cysteine) acts as a nucleophile and a peptide carbonyl group (C) an elcetrophile; in the majority of the cases the two atoms belong to the same residue. The S...C distance is shorter than the sum of the respective van der Waals radii; there is a direct correlation between this length and the angular deviation of the S-C vector from the normal to the carbonyl plane. Other systematics have also been identified. This interaction changes the normal distribution of the conformation of the cysteine side-chain. Besides providing stability to metalloproteins such an interaction is likely to modulate the redox potential of the metal center.

1) Bürgi, H.B., Dunitz, J.D. and Shefter, E. (1973) J. Am. Chem. Soc. 95, 5065-5067.