Non-hydrogen bond interactions involving the methionine sulfur atom

Of all the nonbonded interactions, hydrogen bond, because of its geometry i nvolving polar atoms, is the most easily recognizable. Here we characterize two interactions involving the divalent sulfur of methionine (Met) residue s that do not need any participation of proton. In one an oxygen atom of th e main-chain carbonyl group or a carboxylate side chain is used. In another an aromatic atom interacting along the face of the ring is utilized. In th ese, the divalent sulfur behaves as an electrophile and the other electron- rich atom, a nucleophile. The stereochemistry of the interaction is such th at the nucleophile tends to approach approximately along the extension of o ne of the covalent bonds to S. The nitrogen atom of histidine side chain is extensively used in these nonbonded contacts. There is no particular geome tric pattern in the interaction of S with the edge of an aromatic ring, exc ept when an N-H group in involved, which is found within 40 degrees from th e perpendicular to the sulfide plane, thus defining the geometry of hydroge n bond interaction involving the sulfur atom. As most of the Met residues w hich partake in such stereospecific interactions are buried, these would be important for the stability of the protein core, and their incorporation i n the binding site would be useful for molecular recognition and optimizati on of the site's affinity for partners (especially containing aromatic and heteroaromatic groups). Mutational studies aimed at replacing Met by other residues would benefit from the delineation of these interactions.