Modeling and structural analysis of PA clan serine proteasesReport as inadecuate




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BMC Research Notes

, 5:256

First Online: 24 May 2012Received: 14 December 2011Accepted: 11 May 2012DOI: 10.1186-1756-0500-5-256

Cite this article as: Laskar, A., Rodger, E.J., Chatterjee, A. et al. BMC Res Notes 2012 5: 256. doi:10.1186-1756-0500-5-256

Abstract

BackgroundSerine proteases account for over a third of all known proteolytic enzymes; they are involved in a variety of physiological processes and are classified into clans sharing structural homology. The PA clan of endopeptidases is the most abundant and over two thirds of this clan is comprised of the S1 family of serine proteases, which bear the archetypal trypsin fold and have a catalytic triad in the order Histidine, Aspartate, Serine. These proteases have been studied in depth and many three dimensional structures have been experimentally determined. However, these structures mostly consist of bacterial and animal proteases, with a small number of plant and fungal proteases and as yet no structures have been determined for protozoa or archaea. The core structure and active site geometry of these proteases is of interest for many applications. This study investigated the structural properties of different S1 family serine proteases from a diverse range of taxa using molecular modeling techniques.

ResultsOur predicted models from protozoa, archaea, fungi and plants were combined with the experimentally determined structures of 16 S1 family members and used for analysis of the catalytic core. Amino acid sequences were submitted to SWISS-MODEL for homology-based structure prediction or the LOOPP server for threading-based structure prediction. 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. Some highly conserved residues potentially contributing to the stability of the structural core were identified. 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.

ConclusionsEncompassing a wide range of taxa, our structural analysis provides an evolutionary perspective on S1 family serine proteases. Focusing on the common core containing the catalytic site of the enzyme, this analysis is beneficial for future molecular modeling strategies and structural analysis of serine protease models.

KeywordsSerine protease PA clan Homology Threading Modeling Electronic supplementary materialThe online version of this article doi:10.1186-1756-0500-5-256 contains supplementary material, which is available to authorized users.

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Author: Aparna Laskar - Euan J Rodger - Aniruddha Chatterjee - Chhabinath Mandal

Source: https://link.springer.com/







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