Journal of Molecular Evolution

, Volume 48, Issue 2, pp 125–132

Accelerated Evolution and Molecular Surface of Venom Phospholipase A2 Enzymes

  • R. Manjunatha  Kini
  • Yiu Man  Chan
Article

DOI: 10.1007/PL00006450

Cite this article as:
Kini, R. & Chan, Y. J Mol Evol (1999) 48: 125. doi:10.1007/PL00006450

Abstract.

Multiple phospholipase A2 (PLA2) isoenzymes found in a single snake venom induce a variety of pharmacological effects. These multiple forms are formed by gene duplication and accelerated evolution of exons. We examined the amino acid sequences of 127 snake venom PLA2 enzymes and their homologues to study in which location most natural substitutions occur. Our data show that hot spots of amino acid substitutions in this group of proteins occur mostly on the surface. A logistic model correlating the substitution rates of each amino acid residue with their surface accessibility indicates that the probability of natural substitutions occurring in the fully exposed residue is 2.6–3.5 times greater than that of substitutions occurring in buried residues. These surface substitutions play a significant role in the evolution of new PLA2 isoenzymes by altering the specificity of targeting to various tissues or cells, resulting in distinct pharmacological effects. Thus natural substitutions in PLA2 enzymes, in contrast to popular belief, are not random substitutions but appear to be directed toward modifying the molecular surface.

Key words: Protein evolution — Snake venom — Surface accessibility — Natural substitutions — Toxin — Pharmacological effects

Copyright information

© Springer-Verlag New York Inc. 1999

Authors and Affiliations

  • R. Manjunatha  Kini
    • 1
  • Yiu Man  Chan
    • 3
  1. 1.Bioscience Centre, Faculty of Science, National University of Singapore, 10, Kent Ridge Crescent, Singapore 119260Singapore
  2. 2.Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0614, USAUSA
  3. 3.Department of Mathematics, Faculty of Science, National University of Singapore, 10, Kent Ridge Crescent, Singapore 119260Singapore