4ny4

Crystal structure of CYP3A4 in complex with an inhibitor

spinqualitylabelsall models 4ny4, resolution 2.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ny4 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 2.95Å Ligands: 2QH, HEM 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 Cytochrome P450 (CYP) enzymes are key players in xenobiotic metabolism, and inhibition of CYPs can therefore result in unwanted drug-drug interactions. Within drug discovery, CYP inhibition can cause delays in the progression of candidate drugs, or even premature closure of projects. During the past decade, a massive effort in the pharmaceutical industry and academic research has produced a wealth of structural information in the CYP field. In this short review, we will describe how structure-based approaches can be used in the pharmaceutical industry to work away from CYP inhibition, with a focus on the opportunities and challenges. We will show two examples from our own work where structural information on CYP2C9 and CYP3A4 inhibitor complexes have been successfully exploited in ongoing drug discovery projects. Structure-based ligand design to overcome CYP inhibition in drug discovery projects.,Branden G, Sjogren T, Schnecke V, Xue Y Drug Discov Today. 2014 Jul;19(7):905-911. doi: 10.1016/j.drudis.2014.03.012., Epub 2014 Mar 16. PMID:24642031 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also CYP3A4 Cytochrome P450 3D structures

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