![]() ![]() Subsequently, we used CLASP to quantify promiscuous activities in a wide range of proteins. We previously presented a bottom-up method for active site prediction (CLASP) using active site residues. ![]() We selected proteases with known active sites and 3D structures from each family listed in MEROPS and encapsulated their active site motifs into a single protease search module. The abundance of proteolytic enzymes in biological systems results from the varied physiological conditions under which these enzymes have evolved to be effective. The MEROPS database systematically categorizes these protein families and clans to provide an integrated information source. Proteolytic enzymes catalyze the cleavage of peptide bonds in proteins and are divided into several major classes based on their mechanism of catalysis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. BA extends gratitude to the Icelandic National Research Council and the University of Iceland Research Found for supporting the project financially. BFU 2007/62062, and the University of the Basque Country for grant No. FMG thanks the Spanish Ministerio de Ciencia e Innovacion for grant No. MO was supported in part by a Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (grant No. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: BJR would like to thank the Tata Institute of Fundamental Research (Department of Atomic Energy) for financial support. Received: Accepted: JPublished: August 5, 2013Ĭopyright: © 2013 Rendón-Ramirez et al. Uversky, University of South Florida College of Medicine, United States of America (2013) A Computational Module Assembled from Different Protease Family Motifs Identifies PI PLC from Bacillus cereus as a Putative Prolyl Peptidase with a Serine Protease Scaffold. Thus, we propose a computational method of extending protein families based on the spatial and electrostatic congruence of active site residues.Ĭitation: Rendón-Ramírez A, Shukla M, Oda M, Chakraborty S, Minda R, Dandekar AM, et al. Edman degradation analysis linked the specificity of the protease activity to a proline in the amino terminal, suggesting that the PI-PLC is a prolyl peptidase. This was validated by protease assays, mass spectrometry and by inhibition of the native phospholipase activity of PI-PLC by the well-known serine protease inhibitor AEBSF (IC50 = 0.018 mM). Our analysis indicated that phosphoinositide-specific PLC from Bacillus cereus is a serine protease. ![]() Since APs and proteases are an integral component of outer membrane vesicles (OMV), we sought to query other OMV proteins, like phospholipase C (PLC), using this search module. Here, we assemble a module which encapsulates the multifarious motifs used by protease families listed in the MEROPS database. Subsequently, we defined a methodology to quantify promiscuous activities in a wide range of proteins. CLASP identified a promiscuous serine protease scaffold in alkaline phosphatases (AP) and a scaffold recognizing a β-lactam (imipenem) in a cold-active Vibrio AP. We have previously established a computational method to detect functions in proteins based on the spatial and electrostatic properties of the catalytic residues (CLASP). While a BLAST search on these proteases identifies homologous proteins, sequence alignment methods often fail to identify relationships arising from convergent evolution, exon shuffling, and modular reuse of catalytic units. These distinct types have been systematically categorized in the MEROPS database. Proteolytic enzymes have evolved several mechanisms to cleave peptide bonds. ![]()
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