3wek

Crystal structure of the human squalene synthase F288L mutant in complex with presqualene pyrophosphate

spinqualitylabelsall models 3wek, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wek 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 1.85Å Ligands: MG, PS7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FDFT_HUMAN Publication Abstract from PubMed Squalene synthase (SQS) is a divalent metal-ion-dependent enzyme that catalyzes the two-step reductive `head-to-head' condensation of two molecules of farnesyl pyrophosphate to form squalene using presqualene diphosphate (PSPP) as an intermediate. In this paper, the structures of human SQS and its mutants in complex with several substrate analogues and intermediates coordinated with Mg2+ or Mn2+ are presented, which stepwise delineate the biosynthetic pathway. Extensive study of the SQS active site has identified several critical residues that are involved in binding reduced nicotinamide dinucleotide phosphate (NADPH). Based on mutagenesis data and a locally closed (JK loop-in) structure observed in the hSQS-(F288L)-PSPP complex, an NADPH-binding model is proposed for SQS. The results identified four major steps (substrate binding, condensation, intermediate formation and translocation) of the ordered sequential mechanisms involved in the `1'-1' isoprenoid biosynthetic pathway. These new findings clarify previous hypotheses based on site-directed mutagenesis and biochemical analysis. Structural insights into the catalytic mechanism of human squalene synthase.,Liu CI, Jeng WY, Chang WJ, Shih MF, Ko TP, Wang AH Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):231-41. doi:, 10.1107/S1399004713026230. Epub 2014 Jan 17. PMID:24531458 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Squalene synthase

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