THE OCCURRENCE OF C-H-CENTER-DOT-CENTER-DOT-CENTER-DOT-O HYDROGEN-BONDS IN PROTEINS

Hydrogen bonds are a major feature of protein structure. By a generall y accepted definition, they occur whenever a proton is shared by two e lectronegative atoms. Hence, only Hydrogens bonded to nitrogen and oxy gen atoms are usually considered in analyses of protein hydrogen bond networks. However, X-ray and neutron diffraction studies have shown th at crystals of various organic compounds exhibit close C-H ... X conta cts (where X is an electronegative atom, in most cases oxygen) which s how all the stereochemical hallmarks of hydrogen bonds. In this work, we describe an analysis of short C - H ... O interactions in a sample of known protein structures representing different categories of terti ary folds and refined at a resolution of at least 2 Angstrom. Although our analysis is based on the calculated coordinates of hydrogen atoms , its results are statistically significant: we find strong evidence t hat a large percentage of short C ... O contacts constitute cohesive i nteractions. Moreover, the stereochemical study of C - H ... O = C con tacts, in which the orientation of free electron orbitals on the accep tor oxygen atom can be predicted, reveals that these interactions exhi bit stereochemical features typical of hydrogen bonds. Among the hydro gen atoms involved in these contacts, the most common are those bonded to ct carbon. This is consistent with the fact that these hydrogens a re more acidic than others. We describe four different categories of C - H ... O = C bonds. Those found between C-alpha - H groups and main chain oxygens in adjacent strands of beta sheets are the most ubiquito us. Our results call for a revision of crystallographic restrained ref inement programs which treat close carbon-oxygen contacts as purely re pulsive; they may also have implications for the understanding of some enzymatic reaction mechanisms. (C) 1995 Academic Press Limited