5a1r

Crystal structure of cytochrome P450 3A4 bound to progesteroneCrystal structure of cytochrome P450 3A4 bound to progesterone

Structural highlights 5a1r is a 1 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 2.45Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CP3A4_HUMAN Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide. Publication Abstract from PubMed We co-crystallized human cytochrome P450 3A4 (CYP3A4) with progesterone (PRG) under two different conditions, but the resulting complexes contained only one PRG molecule bound to the previously identified peripheral site. A novel feature in one of our structures is a citrate ion, originating from the crystallization solution. The citrate-binding site is located in an area where the N-terminus splits from the protein core and, thus, is suitable for the interaction with the anionic phospholipids of the microsomal membrane. We investigated how citrate affects the function of a soluble CYP3A4 monooxygenase system consisting of equimolar amounts of CYP3A4 and cytochrome P450 reductase (CPR). Citrate was found to affect the properties of both redox partners and stimulated their catalytic activities in a concentration-dependent manner via a complex mechanism. CYP3A4-substrate binding, reduction of CPR with NADPH, and interflavin and interprotein electron transfer were identified as citrate-sensitive steps. Comparative analysis of various negatively charged organic compounds indicated that, in addition to alterations caused by changes in ionic strength, anions modulate the properties of CYP3A4 and CPR through specific anion-protein interactions. Our results help to better understand previous observations and provide new mechanistic insights into CYP3A4 function. Anion-Dependent Stimulation of CYP3A4 Monooxygenase.,Sevrioukova IF, Poulos TL Biochemistry. 2015 Jun 23. PMID:26066995 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

spinqualitylabelsall models 5a1r, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image