Protein Engineering, Vol. 16, No. 3, 201-207,
March 2003
© 2003 Oxford University Press
Close pairs of carboxylates: a possibility of multicenter hydrogen bonds in proteins
1 Biology Department, 402 Kell Hall, GSU, 24 Peachtree Center Avenue, and 4 Computer Science Department, Georgia State University, Atlanta, GA 30303, USA and 2 Department of Chemistry, Moscow State University, 119899 Moscow, Russia
3 To whom correspondence should be addressed, at the first address. E-mail: biotiy{at}suez.cs.gsu.edu
Covalent attachment of hydrogen to the donor atom may be not an essential characteristic of stable hydrogen bonds. A positively charged particle (such as a proton), located between the two negatively charged residues, may lead to a stable interaction of the two negative residues. This paper analyzes close Asp–Glu pairs of residues in a large set of protein chains; 840 such pairs of residues were identified, of which 28% were stabilized by a metal ion, 12% by a positive residue nearby and 60% are likely to be stabilized by a proton. The absence of apparent structural constraints, secondary structure preferences, somewhat lower B-factors and a distinct correlation between pH and the minimal O–O distance in carboxylate pairs suggest that most of the abnormally close pairs could indeed be stabilized by a shared proton. Implications for protein stability and modeling are discussed.