Human thromboxane A2 receptor genetic variants: in silico, in vitro and "in platelet" analysis.

ABSTRACT: Thromboxane and its receptor have emerged as key players in modulating vascular thrombotic events. Thus, a dysfunctional hTP genetic variant may protect against (hypoactivity) or promote (hyperactivity) vascular events, based upon its activity on platelets. After extensive in silico analysis, six hTP-α variants were selected (C(68)S, V(80)E, E(94)V, A(160)T, V(176)E, and V(217)I) for detailed biochemical studies based on structural proximity to key regions involved in receptor function and in silico predictions. Variant biochemical profiles ranged from severe instability (C(68)S) to normal (V(217)I), with most variants demonstrating functional alteration in binding, expression or activation (V(80)E, E(94)V, A(160)T, and V(176)E). In the absence of patient platelet samples, we developed and

SUBMITTER: Gleim S 

PROVIDER: S-EPMC3696120 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature