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2zcp

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{{STRUCTURE_2zcp| PDB=2zcp | SCENE= }}
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'''Crystal structure of the C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus complexed with farnesyl thiopyrophosphate'''
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===Crystal structure of the C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus complexed with farnesyl thiopyrophosphate===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_18276850}}
==About this Structure==
==About this Structure==
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[[Category: Staphyloxanthin biosynthesis]]
[[Category: Staphyloxanthin biosynthesis]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 20:09:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:09:03 2008''

Revision as of 01:09, 29 July 2008

Image:2zcp.png

Template:STRUCTURE 2zcp

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

Template:ABSTRACT PUBMED 18276850

About this Structure

2ZCP is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.

Reference

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

Page seeded by OCA on Tue Jul 29 04:09:03 2008

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