4quv | pdb_00004quv

Structure of an integral membrane delta(14)-sterol reductase

spinqualitylabelsall models 4quv, resolution 2.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4quv is a 2 chain structure with sequence from Methylotuvimicrobium alcaliphilum 20Z. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ERG_META2 Reduces the C14=C15 double bond of 4,4-dimethyl-cholesta-8,14,24-trienol to produce 4,4-dimethyl-cholesta-8,24-dienol. Complements the deletion of the Delta(14)-sterol reductase gene ERG24 in yeast. Publication Abstract from PubMed Sterols are essential biological molecules in the majority of life forms. Sterol reductases including Delta14-sterol reductase (C14SR, also known as TM7SF2), 7-dehydrocholesterol reductase (DHCR7) and 24-dehydrocholesterol reductase (DHCR24) reduce specific carbon-carbon double bonds of the sterol moiety using a reducing cofactor during sterol biosynthesis. Lamin B receptor (LBR), an integral inner nuclear membrane protein, also contains a functional C14SR domain. Here we report the crystal structure of a Delta14-sterol reductase (MaSR1) from the methanotrophic bacterium Methylomicrobium alcaliphilum 20Z (a homologue of human C14SR, LBR and DHCR7) with the cofactor NADPH. The enzyme contains ten transmembrane segments (TM1-10). Its catalytic domain comprises the carboxy-terminal half (containing TM6-10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer. Comparison with a soluble steroid 5beta-reductase structure suggests that the reducing end of NADPH meets the sterol substrate at the juncture of the two pockets. A sterol reductase activity assay proves that MaSR1 can reduce the double bond of a cholesterol biosynthetic intermediate, demonstrating functional conservation to human C14SR. Therefore, our structure as a prototype of integral membrane sterol reductases provides molecular insight into mutations in DHCR7 and LBR for inborn human diseases. Structure of an integral membrane sterol reductase from Methylomicrobium alcaliphilum.,Li X, Roberti R, Blobel G Nature. 2014 Oct 12. doi: 10.1038/nature13797. PMID:25307054 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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