3w7f

Crystal structure of the C(30) carotenoid dehydrosqualene synthase from staphylococcus aureus complexed with farnesyl thiopyrophosphate

spinqualitylabelsall models 3w7f, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3w7f is a 2 chain structure with sequence from Staphylococcus aureus. This structure supersedes the now removed PDB entry 2zcp. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.25Å Ligands: FPS, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CRTM_STAAU Publication Abstract from PubMed Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. aureus posing a serious public health threat. The golden carotenoid pigment of S. aureus, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures of S. aureus dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural similarity to human squalene synthase (SQS). We screened nine SQS inhibitors and determined the structures of three, bound to CrtM. One, previously tested for cholesterol-lowering activity in humans, blocked staphyloxanthin biosynthesis in vitro (median inhibitory concentration approximately 100 nM), resulting in colorless bacteria with increased susceptibility to killing by human blood and to innate immune clearance in a mouse infection model. This finding represents proof of principle for a virulence factor-based therapy against S. aureus. A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence.,Liu CI, Liu GY, Song Y, Yin F, Hensler ME, Jeng WY, Nizet V, Wang AH, Oldfield E Science. 2008 Mar 7;319(5868):1391-4. Epub 2008 Feb 14. PMID:18276850 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Squalene synthase

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