Protein Science
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online before print May 20, 2008, 10.1110/ps.034801.108
Protein Science (2008), 17:1354-1361. Published by Cold Spring Harbor Laboratory Press. Copyright © 2008 The Protein Society
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Research Data
Right arrow All Versions of this Article:
ps.034801.108v1
17/8/1354    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Chandrasekaran, V.
Right arrow Articles by Pedersen, L. G.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chandrasekaran, V.
Right arrow Articles by Pedersen, L. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Computational study of the putative active form of protein Z (PZa): Sequence design and structural modeling

Vasu Chandrasekaran1,3, Chang Jun Lee1,3, Robert E. Duke1,2, Lalith Perera2, and Lee G. Pedersen1,2

1 Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
2 Laboratory of Structural Biology, National Institute of Environmental Health Sciences-National Institutes of Health, Research Triangle Park, North Carolina 27709, USA

(RECEIVED February 4, 2008; FINAL REVISION May 5, 2008; ACCEPTED May 7, 2008)

Although protein Z (PZ) has a domain arrangement similar to the essential coagulation proteins FVII, FIX, FX, and protein C, its serine protease (SP)-like domain is incomplete and does not exhibit proteolytic activity. We have generated a trial sequence of putative activated protein Z (PZa) by identifying amino acid mutations in the SP-like domain that might reasonably resurrect the serine protease catalytic activity of PZ. The structure of the activated form was then modeled based on the proposed sequence using homology modeling and solvent-equilibrated molecular dynamics simulations. In silico docking of inhibitors of FVIIa and FXa to the putative active site of equilibrated PZa, along with structural comparison with its homologous proteins, suggest that the designed PZa can possibly act as a serine protease.

Keywords: protein Z (PZ); sequence design; active form of protein Z (PZa); homology modeling; molecular dynamics simulation; molecular docking


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by The Protein Society.