Analysis of pH-dependent elements in proteins: geometry and properties of pairs of hydrogen-bonded carboxylic acid side-chains - PubMed (original) (raw)
. 2005 Feb 1;58(2):396-406.
doi: 10.1002/prot.20328.
Affiliations
- PMID: 15558575
- DOI: 10.1002/prot.20328
Analysis of pH-dependent elements in proteins: geometry and properties of pairs of hydrogen-bonded carboxylic acid side-chains
Gerd Wohlfahrt. Proteins. 2005.
Abstract
A rather frequent but so far little discussed observation is that pairs of carboxylic acid side-chains in proteins can share a proton in a hydrogen bond. In the present article, quantum chemical calculations of simple model systems for carboxyl-carboxylate interactions are compared with structural observations from proteins. A detailed structural analysis of the proteins deposited in the PDB revealed that, in a subset of proteins sharing less than 90% sequence identity, 19% (314) contain at least one pair of carboxylic acids with their side-chain oxygen atoms within hydrogen-bonding distance. As the distance between those interacting oxygen atoms is frequently very short ( approximately 2.55 A), many of these carboxylic acids are suggested to share a proton in a strong hydrogen bond. When situated in an appropriate structural environment (low dielectric constant), some might even form a low barrier hydrogen bond. The quantum chemical studies show that the most frequent geometric features of carboxyl-carboxylate pairs found in proteins, and no or symmetric ligation, are also the most stable arrangements at low dielectric constants, and they also suggest at medium and low pH a higher stability than for isosteric amide-carboxylate pairs. The presence of these pairs in 119 different enzymes found in the BRENDA database is set in relation to their properties and functions. This analysis shows that pH optima of enzymes with carboxyl-carboxylate pairs are shifted to lower than average values, whereas temperature optima seem to be increased. The described structural principles can be used as guidelines for rational protein design (e.g., in order to improve pH or temperature stability).
(c) 2004 Wiley-Liss, Inc.
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