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In‐Silico Comparative Structural Analysis of Human and Murine Cyclooxygenase‐2 (Cox‐2)
Author(s) -
Hari Saran Krishnan,
Boluwaduro Adeyemi,
Gautham Sakthi,
Villanueva James Amador
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb76
Subject(s) - in silico , arachidonic acid , inflammation , cyclooxygenase , chemistry , thromboxanes , metabolite , docking (animal) , biochemistry , enzyme , biology , computational biology , immunology , medicine , gene , nursing
Cyclooxygenase 2 (COX2) is a major enzymatic mediator of inflammation that catalyzes the formation of a host of prostaglandins, leukotrienes and thromboxanes. Inflammation is a principal component of a vast range of pathologic processes, ranging from simple infections to malignant neoplasms. Since this physiologic response is sometimes more damaging than beneficial to the human body, curbing its excesses by controlling the activity of COX2 is of great clinical importance. In‐silico studies have utilized murine, bovine, or other forms of COX2, as the human COX‐2 crystal structure has only been very recently elucidated. Using molecular docking and alignment studies, we found differences in the bonding interactions of murine COX2, and a recently resolved human COX2 crystal structure with their substrate, arachidonic acid, as well as piceatannol. Piceatannol is a metabolite of resveratrol, which is found in red wine. Our experiments show that although the sequence and structures of human and murine COX2 are largely similar with variation of 12%, there are important differences in the way their binding sites interact with ligands, with respect to binding energies and amino acid involvement. These differences may become significant in the search and design of small molecules that can function to inhibit the activity of COX‐2. Clinically, this would translate to better control over the deleterious effects of inflammation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .