alexa Three-dimensional models of four mouse mast cell chymases. Identification of proteoglycan binding regions and protease-specific antigenic epitopes.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Sali A, Matsumoto R, McNeil HP, Karplus M, Stevens RL

Abstract Share this page

Abstract Mouse mast cell protease (mMCP) 1, mMCP-2, mMCP-4, and mMCP-5 are serine proteases which are predicted to have chymotryptic specificity (chymases). They are bound to negatively charged heparin or chondroitin sulfate proteoglycans and are stored in secretory granules. Three-dimensional (3D) models of these four proteases were constructed with a comparative molecular modeling technique based on satisfaction of spatial constraints. The models were used to predict immunogenic epitopes and surface regions that are likely to interact with proteoglycans. Nine potential antigenic segments in the four chymases were identified on the basis of solvent accessibility, protrusion, flexibility, and sequence variability. These segments are suitable epitopes for preparation of protease-specific antipeptide immunoglobulin. Two regions with net charges ranging from +6 to +10 at neutral pH were found on the surfaces of mMCP-4 and mMCP-5. The two regions are located far from the substrate binding cleft at diametrically opposite ends of the folded proteases. A strong positive electrostatic potential surrounds the two regions. Thus, they are good candidates for binding sites that interact with heparin proteoglycan in the granules of serosal mast cells. In contrast, mMCP-1 and mMCP-2, which are present in granules of mucosal mast cells that contain chondroitin sulfate, lack one of these regions and have a lower charge density in the other. The differences between the 3D models provide a structural basis for the selective localization of specific chymases within mouse mast cells that contain different proteoglycans.
This article was published in J Biol Chem and referenced in Journal of Proteomics & Bioinformatics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 9th International Conference on Bioinformatics
    October 23-24, 2017 Paris, France
  • 9th International Conference and Expo on Proteomics
    October 23-25, 2017 Paris, France

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords