1p42
From Proteopedia
(New page: 200px<br /><applet load="1p42" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p42, resolution 2.00Å" /> '''Crystal structure of...) |
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| - | [[Image:1p42.gif|left|200px]]<br /><applet load="1p42" size=" | + | [[Image:1p42.gif|left|200px]]<br /><applet load="1p42" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1p42, resolution 2.00Å" /> | caption="1p42, resolution 2.00Å" /> | ||
'''Crystal structure of Aquifex aeolicus LpxC Deacetylase (Zinc-Inhibited Form)'''<br /> | '''Crystal structure of Aquifex aeolicus LpxC Deacetylase (Zinc-Inhibited Form)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The outer leaflet of the outer membrane of the Gram-negative bacterium | + | The outer leaflet of the outer membrane of the Gram-negative bacterium serves as a permeability barrier and is composed of lipopolysaccharide, also known as endotoxin. The membrane anchor of lipopolysaccharide is lipid A, the biosynthesis of which is essential for cell viability. The first committed step in lipid A biosynthesis is catalyzed by UDP-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase (LpxC), a zinc-dependent deacetylase. Here we report the crystal structure of LpxC from Aquifex aeolicus, which reveals a new alpha+beta fold reflecting primordial gene duplication and fusion, as well as a new zinc-binding motif. The catalytic zinc ion resides at the base of an active-site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid. This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents. Notably, simple inhibitors designed to target interactions in the hydrophobic tunnel bind with micromolar affinity, thereby representing a step toward the structure-based design of a potent, broad-spectrum antibacterial drug. |
==About this Structure== | ==About this Structure== | ||
| - | 1P42 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with ZN and MYR as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1P42 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=MYR:'>MYR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P42 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Aquifex aeolicus]] | [[Category: Aquifex aeolicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
| - | [[Category: Fierke, C | + | [[Category: Fierke, C A.]] |
| - | [[Category: Rusche, K | + | [[Category: Rusche, K M.]] |
[[Category: Shin, H.]] | [[Category: Shin, H.]] | ||
| - | [[Category: Whittington, D | + | [[Category: Whittington, D A.]] |
[[Category: MYR]] | [[Category: MYR]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: hydrophobic tunnel]] | [[Category: hydrophobic tunnel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:24:51 2008'' |
Revision as of 12:24, 21 February 2008
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Crystal structure of Aquifex aeolicus LpxC Deacetylase (Zinc-Inhibited Form)
Overview
The outer leaflet of the outer membrane of the Gram-negative bacterium serves as a permeability barrier and is composed of lipopolysaccharide, also known as endotoxin. The membrane anchor of lipopolysaccharide is lipid A, the biosynthesis of which is essential for cell viability. The first committed step in lipid A biosynthesis is catalyzed by UDP-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase (LpxC), a zinc-dependent deacetylase. Here we report the crystal structure of LpxC from Aquifex aeolicus, which reveals a new alpha+beta fold reflecting primordial gene duplication and fusion, as well as a new zinc-binding motif. The catalytic zinc ion resides at the base of an active-site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid. This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents. Notably, simple inhibitors designed to target interactions in the hydrophobic tunnel bind with micromolar affinity, thereby representing a step toward the structure-based design of a potent, broad-spectrum antibacterial drug.
About this Structure
1P42 is a Single protein structure of sequence from Aquifex aeolicus with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis., Whittington DA, Rusche KM, Shin H, Fierke CA, Christianson DW, Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8146-50. Epub 2003 Jun 20. PMID:12819349
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