|
|
| (5 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:2zcp.jpg|left|200px]] | + | #REDIRECT [[3w7f]] This PDB entry is obsolete and replaced by 3w7f |
| - | | + | |
| - | {{Structure
| + | |
| - | |PDB= 2zcp |SIZE=350|CAPTION= <scene name='initialview01'>2zcp</scene>, resolution 2.25Å
| + | |
| - | |SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Residue+A+661'>AC1</scene>, <scene name='pdbsite=AC2:Mg+Binding+Site+For+Residue+A+662'>AC2</scene>, <scene name='pdbsite=AC3:Mg+Binding+Site+For+Residue+A+663'>AC3</scene>, <scene name='pdbsite=AC4:Mg+Binding+Site+For+Residue+B+664'>AC4</scene>, <scene name='pdbsite=AC5:Mg+Binding+Site+For+Residue+B+665'>AC5</scene>, <scene name='pdbsite=AC6:Mg+Binding+Site+For+Residue+B+666'>AC6</scene>, <scene name='pdbsite=AC7:Fps+Binding+Site+For+Residue+A+657'>AC7</scene>, <scene name='pdbsite=AC8:Fps+Binding+Site+For+Residue+A+658'>AC8</scene>, <scene name='pdbsite=AC9:Fps+Binding+Site+For+Residue+B+659'>AC9</scene> and <scene name='pdbsite=BC1:Fps+Binding+Site+For+Residue+B+660'>BC1</scene>
| + | |
| - | |LIGAND= <scene name='pdbligand=FPS:S-[(2E,6E)-3,7,11-TRIMETHYLDODECA-2,6,10-TRIENYL]+TRIHYDROGEN+THIODIPHOSPHATE'>FPS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
| + | |
| - | |ACTIVITY=
| + | |
| - | |GENE= CrtM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])
| + | |
| - | |DOMAIN=
| + | |
| - | |RELATEDENTRY=[[2zco|2ZCO]], [[2zcq|2ZCQ]], [[2zcr|2ZCR]], [[2zcs|2ZCS]]
| + | |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zcp OCA], [http://www.ebi.ac.uk/pdbsum/2zcp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2zcp RCSB]</span>
| + | |
| - | }}
| + | |
| - | | + | |
| - | '''Crystal structure of the C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus complexed with farnesyl thiopyrophosphate'''
| + | |
| - | | + | |
| - | | + | |
| - | ==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==
| + | |
| - | 2ZCP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZCP 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:[http://www.ncbi.nlm.nih.gov/pubmed/18276850 18276850]
| + | |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Staphylococcus aureus]]
| + | |
| - | [[Category: Jeng, W Y.]]
| + | |
| - | [[Category: Liu, C I.]]
| + | |
| - | [[Category: Oldfield, E.]]
| + | |
| - | [[Category: Wang, A H.]]
| + | |
| - | [[Category: carotenoid biosynthesis]]
| + | |
| - | [[Category: crtm]]
| + | |
| - | [[Category: farnesyl pyrophosphate]]
| + | |
| - | [[Category: farnesyl thiopyrophosphate]]
| + | |
| - | [[Category: fspp]]
| + | |
| - | [[Category: head-to-head condensation]]
| + | |
| - | [[Category: staphyloxanthin biosynthesis]]
| + | |
| - | [[Category: transferase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:20:30 2008''
| + | |
