Table of Contents
Journal of Amino Acids
Volume 2011, Article ID 606797, 10 pages
Review Article

Serpin Inhibition Mechanism: A Delicate Balance between Native Metastable State and Polymerization

1Department of Biosciences, Jamia Millia Islamia University, Jamia Nagar, New Delhi 110025, India
2Department of Biotechnology, National Institute of Technology Calicut (NITC), NIT Campus P.O., Calicut, Kerala 673601, India

Received 14 February 2011; Accepted 7 March 2011

Academic Editor: Zulfiqar Ahmad

Copyright © 2011 Mohammad Sazzad Khan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The serpins (serine proteinase inhibitors) are structurally similar but functionally diverse proteins that fold into a conserved structure and employ a unique suicide substrate-like inhibitory mechanism. Serpins play absolutely critical role in the control of proteases involved in the inflammatory, complement, coagulation and fibrinolytic pathways and are associated with many conformational diseases. Serpin's native state is a metastable state which transforms to a more stable state during its inhibitory mechanism. Serpin in the native form is in the stressed (S) conformation that undergoes a transition to a relaxed (R) conformation for the protease inhibition. During this transition the region called as reactive center loop which interacts with target proteases, inserts itself into the center of β-sheet A to form an extra strand. Serpin is delicately balanced to perform its function with many critical residues involved in maintaining metastability. However due to its typical mechanism of inhibition, naturally occurring serpin variants produces conformational instability that allows insertion of RCL of one molecule into the β-sheet A of another to form a loop-sheet linkage leading to its polymerization and aggregation. Thus understanding the molecular basis and amino acid involved in serpin polymerization mechanism is critical to devising strategies for its cure.