Statistical Conservation Analysis of Zinc-interacting Residues

As a result of rapid advances in genome sequencing, the pace of discovery of new protein sequences has surpassed that of structure/function determination by orders of magnitude. This is also true for metal-binding proteins, i.e. proteins that bind one or more metal atoms necessary for their biological function. With regard to metal-interacting residues, the question arising is whether these interactions apply additional evolutionary constraints and to what extent. We try to answer this question for a subset of metal-binding-proteins, namely zinc-binding proteins, which play an important role in a number of biological processes, as exemplified by the tumor-suppressor protein p53. Our results shows significantly higher evolutionary pressure on zinc-interacting residues, a result which can be used in a number of other studies, including zinc-binding site prediction.