2iag

Crystal structure of human prostacyclin synthase

spinqualitylabelsall models 2iag, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2iag is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Ligands: HEM, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PTGIS_HUMAN Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Prostacyclin synthase (PGIS) catalyzes an isomerization of prostaglandin H(2) to prostacyclin, a potent mediator of vasodilation and anti-platelet aggregation. Here, we report the crystal structure of human PGIS at 2.15 A resolution, which represents the first three-dimensional structure of a class III cytochrome P450. While notable sequence divergence has been recognized between PGIS and other P450s, PGIS exhibits the typical triangular prism-shaped P450 fold with only moderate structural differences. The conserved acid-alcohol pair in the I helix of P450s is replaced by residues G286 and N287 in PGIS, but the distinctive disruption of the I helix and the presence of a nearby water channel remain conserved. The side-chain of N287 appears to be positioned to facilitate the endoperoxide bond cleavage, suggesting a functional conservation of this residue in O-O bond cleavage. A combination of bent I helix and tilted B' helix creates a channel extending from the heme distal pocket, which seemingly allows binding of various ligands; however, residue W282, placed in this channel at a distance of 8.4 A from the iron with its indole side-chain lying parallel with the porphyrin plane, may serve as a threshold to exclude most ligands from binding. Additionally, a long "meander" region protruding from the protein surface may impede electron transfer. Although the primary sequence of the PGIS cysteine ligand loop diverges significantly from the consensus, conserved tertiary structure and hydrogen bonding pattern are observed for this region. The substrate-binding model was constructed and the structural basis for prostacyclin biosynthesis is discussed. Crystal structure of the human prostacyclin synthase.,Chiang CW, Yeh HC, Wang LH, Chan NL J Mol Biol. 2006 Dec 1;364(3):266-74. Epub 2006 Sep 20. PMID:17020766 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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