%0 Journal Article
%T Three-Dimensional Molecular Modeling of a Diverse Range of SC Clan Serine Proteases
%A Aparna Laskar
%A Aniruddha Chatterjee
%A Somnath Chatterjee
%A Euan J. Rodger
%J Molecular Biology International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/580965
%X Serine proteases are involved in a variety of biological processes and are classified into clans sharing structural homology. Although various three-dimensional structures of SC clan proteases have been experimentally determined, they are mostly bacterial and animal proteases, with some from archaea, plants, and fungi, and as yet no structures have been determined for protozoa. To bridge this gap, we have used molecular modeling techniques to investigate the structural properties of different SC clan serine proteases from a diverse range of taxa. Either SWISS-MODEL was used for homology-based structure prediction or the LOOPP server was used for threading-based structure prediction. The predicted models were refined using Insight II and SCRWL and validated against experimental structures. Investigation of secondary structures and electrostatic surface potential was performed using MOLMOL. The structural geometry of the catalytic core shows clear deviations between taxa, but the relative positions of the catalytic triad residues were conserved. Evolutionary divergence was also exhibited by large variation in secondary structure features outside the core, differences in overall amino acid distribution, and unique surface electrostatic potential patterns between species. Encompassing a wide range of taxa, our structural analysis provides an evolutionary perspective on SC clan serine proteases. 1. Introduction Serine proteases account for over a third of all known proteolytic enzymes and are involved in a range of physiological processes including digestion, immunity, blood clotting, fibrinolysis, reproduction, and protein folding [1]. The proteolytic mechanism of these proteases involves nucleophilic attack of the carbonyl atom of the substrate peptide bond by a catalytic serine (Ser) residue in the active site of the enzyme. In addition to the nucleophilic Ser residue, this reaction is dependent on other critical amino acids in the catalytic site such as an Aspartate (Asp) and a Histidine (His) that together form what is referred to as the catalytic triad (or a dyad in some cases) [2]. The presence of this catalytic triad in at least four distinct protein folds indicates the same mechanism evolved four separate times during evolution [3]. The MEROPS classification system (http://merops.sanger.ac.uk/) has grouped proteases into families according to statistically significant similarities in the amino acid sequence. These protease families are further grouped into clans that have dissimilar amino acid sequences but typically have structural homology and/or
%U http://www.hindawi.com/journals/mbi/2012/580965/