2zco

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|ACTIVITY=
|ACTIVITY=
|GENE= crtM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])
|GENE= crtM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])
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|DOMAIN=
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|RELATEDENTRY=[[2zcp|2ZCP]], [[2zcq|2ZCQ]], [[2zcr|2ZCR]], [[2zcs|2ZCS]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zco OCA], [http://www.ebi.ac.uk/pdbsum/2zco PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2zco RCSB]</span>
}}
}}
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:53:51 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:20:26 2008''

Revision as of 02:20, 31 March 2008


PDB ID 2zco

Drag the structure with the mouse to rotate
, resolution 1.58Å
Gene: crtM (Staphylococcus aureus)
Related: 2ZCP, 2ZCQ, 2ZCR, 2ZCS


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Crystal structure of the C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus


Overview

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.

About this Structure

2ZCO 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

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