Advance in understanding the biosynthesis of prostacyclin and thromboxane A2 in the endoplasmic reticulum membrane via the cyclooxygenase pathway.
Recent advances in topological and structural characterization of the prostacyclin (PGI(2)) and thromboxane A(2) (TXA(2)) synthases have led to the understanding of the biosynthesis of PGI(2) and TXA(2) at a structural level. This mini-review focuses on the molecular mechanism of the isomerization of the prostaglandin H(2) to PGI(2)and TXA(2) by their synthases in the endoplasmic reticulum (ER) membrane coordinated with cyclooxygenase-1 or -2. This review summarizes the evidences in which the biosynthesis of PGI(2)and TXA(2) are influenced/modulated by the membrane anchor residues of the synthases and the ER membrane itself, and provides the structural basis for engineering the synthases for the next generation of gene therapy and drug designs targeting the specific synthases.
The Vascular Biology Research Center and Division of Hematology, Department of Internal Medicine, The University of Texas Health Science Center, Houston, Texas 77030, USA. kruan@uth.tmc.edu
Ke-He
KH
Ruan
D001665:Binding Sites; D020134:Catalytic Domain; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000201:enzymology*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology; D008958:Models, Molecular; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000032:analysis
D013928:Thromboxane A2; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase