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Title

 

 

 

 

Strand 6B deformation and residues exposure towards N-terminal end of helix B during proteinase inhibition by Serpins 

Authors

Poonam Singh & Mohamad Aman Jairajpuri*

Affiliation

Department of Biosciences, Jamia Millia Islamia University, Jamia Nagar, New Delhi-110025, India 

Email

m_jairajpuri.bi@jmi.ac.in

Phone

091-9971259812

FAX

091-11-26980229

Article Type

Hypothesis

 

Date

Received September 13, 2010; Accepted October 26, 2010; Published January 22, 2011
 

Abstract

Serine Protease inhibitors (Serpins) like antithrombin, antitrypsin, neuroserpin, antichymotrypsin, protein C-inhibitor and plasminogen activator inhibitor is involved in important biological functions like blood coagulation, fibrinolysis, inflammation, cell migration and complement activation. Serpins native state is metastable, which undergoes transformation to a more stable state during the process of protease inhibition. Serpins are prone to conformation defects, however little is known about the factors and mechanisms which promote its conformational change and misfolding. Helix B region in serpins is with several point mutations which result in pathological conditions due to polymerization. Helix B analysis for residue burial and cavity was undertaken to understand its role in serpin structure function. A structural overlap and an accessible surface area analysis showed the deformation of strand 6B and exposure of helix B at N-terminal end in cleaved conformation but not in the native and latent conformation of various inhibitory serpins. A cleaved polymer like conformation of antitrypsin also showed deformation of s6B and helix B exposure. Cavity analysis showed that helix B residues were part of the largest cavity in most of the serpins in the native state which increase in size during the transformation to cleaved and latent states. These data for the first time show the importance of strand 6B deformation and exposure of helix B in smooth insertion of the reactive center loop during serpin inhibition and indicate that helix B exposure due to variants may increase its polymer propensity.  

Keywords

 

serine protease inhibitor; protein aggregation and folding; reactive center loop; a1-antitrypsin; shutter domain; accessible surface area; CASTp. 

Citation

Singh & Jairajpuri, Bioinformation 5(8): 315-319 (2011)

Edited by

Kannan Gunasekaran

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.