1ro5
From Proteopedia
(New page: 200px<br /><applet load="1ro5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ro5, resolution 2.30Å" /> '''Crystal Structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1ro5.gif|left|200px]]<br /><applet load="1ro5" size=" | + | [[Image:1ro5.gif|left|200px]]<br /><applet load="1ro5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ro5, resolution 2.30Å" /> | caption="1ro5, resolution 2.30Å" /> | ||
'''Crystal Structure of the AHL Synthase LasI'''<br /> | '''Crystal Structure of the AHL Synthase LasI'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The LasI/LasR quorum-sensing system plays a pivotal role in virulence gene | + | The LasI/LasR quorum-sensing system plays a pivotal role in virulence gene regulation of the opportunistic human pathogen, Pseudomonas aeruginosa. Here we report the crystal structure of the acyl-homoserine lactone (AHL) synthase LasI that produces 3-oxo-C12-AHL from the substrates 3-oxo-C12-acyl-carrier protein (acyl-ACP) and S-adenosyl-L-methionine. The LasI six-stranded beta sheet platform, buttressed by three alpha helices, forms a V-shaped substrate-binding cleft that leads to a tunnel passing through the enzyme that can accommodate the acyl-chain of acyl-ACP. This tunnel places no apparent restriction on acyl-chain length, in contrast to a restrictive hydrophobic pocket seen in the AHL-synthase EsaI. Interactions of essential conserved N-terminal residues, Arg23, Phe27 and Trp33, suggest that the N-terminus forms an enclosed substrate-binding pocket for S-adenosyl-L-methionine. Analysis of AHL-synthase surface residues identified a binding site for acyl-ACP, a role that was supported by in vivo reporter assay analysis of the mutated residues, including Arg154 and Lys150. This structure and the novel explanation of AHL-synthase acyl-chain-length selectivity promise to guide the design of Pseudomonas aeruginosa-specific quorum-sensing inhibitors as antibacterial agents. |
==About this Structure== | ==About this Structure== | ||
| - | 1RO5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with SO4 and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1RO5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RO5 OCA]. |
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Pseudomonas aeruginosa]] | [[Category: Pseudomonas aeruginosa]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Churchill, M | + | [[Category: Churchill, M E.]] |
| - | [[Category: Gould, T | + | [[Category: Gould, T A.]] |
| - | [[Category: Schweizer, H | + | [[Category: Schweizer, H P.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
| Line 21: | Line 21: | ||
[[Category: phosphopantetheine fold]] | [[Category: phosphopantetheine fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:52:54 2008'' |
Revision as of 12:52, 21 February 2008
|
Crystal Structure of the AHL Synthase LasI
Overview
The LasI/LasR quorum-sensing system plays a pivotal role in virulence gene regulation of the opportunistic human pathogen, Pseudomonas aeruginosa. Here we report the crystal structure of the acyl-homoserine lactone (AHL) synthase LasI that produces 3-oxo-C12-AHL from the substrates 3-oxo-C12-acyl-carrier protein (acyl-ACP) and S-adenosyl-L-methionine. The LasI six-stranded beta sheet platform, buttressed by three alpha helices, forms a V-shaped substrate-binding cleft that leads to a tunnel passing through the enzyme that can accommodate the acyl-chain of acyl-ACP. This tunnel places no apparent restriction on acyl-chain length, in contrast to a restrictive hydrophobic pocket seen in the AHL-synthase EsaI. Interactions of essential conserved N-terminal residues, Arg23, Phe27 and Trp33, suggest that the N-terminus forms an enclosed substrate-binding pocket for S-adenosyl-L-methionine. Analysis of AHL-synthase surface residues identified a binding site for acyl-ACP, a role that was supported by in vivo reporter assay analysis of the mutated residues, including Arg154 and Lys150. This structure and the novel explanation of AHL-synthase acyl-chain-length selectivity promise to guide the design of Pseudomonas aeruginosa-specific quorum-sensing inhibitors as antibacterial agents.
About this Structure
1RO5 is a Single protein structure of sequence from Pseudomonas aeruginosa with and as ligands. Full crystallographic information is available from OCA.
Reference
Structure of the Pseudomonas aeruginosa acyl-homoserinelactone synthase LasI., Gould TA, Schweizer HP, Churchill ME, Mol Microbiol. 2004 Aug;53(4):1135-46. PMID:15306017
Page seeded by OCA on Thu Feb 21 14:52:54 2008
