title: Thromboxane molecules do not adopt the prostaglandin hairpin conformation.
abstract: The hairpin conformational hypothesis has been proposed to rationalise much of the structure-activity and receptor-binding data which have accumulated for the prostaglandin (PG) hormones. The hairpin conformation, thought to be necessary for PG activity, requires that the alpha- and omega-chains of the molecule be extended and in parallel alignment, separated by a van der Waals contact distance for the full length of the chains, with the ends of the chains approximately 5.5 A apart. The similarity between the structures of the thromboxanes (TXs) and the PGs suggests that the profile of activity of TXs, like that of PGs, centres on subtle conformational variation of the hairpin geometry. Thromboxane B2 (TXB2) is a stable hydrolysis product of a highly reactive, short-lived intermediate, thromboxane A2 (TXA2), which is formed from the prostaglandin endoperoxide (PGH2) as indicated in Fig. 1. An examination of molecular models of TXA2 and TXB2 suggests that the structural differences between the ring moieties may have much less influence in altering the side-chain conformation of TXs than do substitutents on the relatively more flexible cyclopentane ring of a PG molecule. We report here the first diffraction analysis of a thromboxane structure and note that the molecular conformation is not hairpin shaped.
mesh_terms: D008968:Molecular Conformation; D011453:Prostaglandins; D013329:Structure-Activity Relationship; D013928:Thromboxane A2; D013929:Thromboxane B2; D013931:Thromboxanes
chemical_list: D011453:Prostaglandins; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2