1ro5: Difference between revisions

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[[Image:1ro5.gif|left|200px]]<br /><applet load="1ro5" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1ro5.gif|left|200px]]<br /><applet load="1ro5" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1ro5, resolution 2.30Å" />

'''Crystal Structure of the AHL Synthase LasI'''<br />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1RO5 OCA].

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==

Line 13:

[[Category: Pseudomonas aeruginosa]]

[[Category: Single protein]]

[[Category: Churchill, M.E.]]

[[Category: Churchill, M E.]]

[[Category: Gould, T.A.]]

[[Category: Gould, T A.]]

[[Category: Schweizer, H.P.]]

[[Category: Schweizer, H P.]]

[[Category: SO4]]

[[Category: ZN]]

Line 21:

[[Category: phosphopantetheine fold]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:52:54 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1ro5.gif|left|200px]]<br /><applet load="1ro5" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ro5.gif|left|200px]]<br /><applet load="1ro5" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ro5, resolution 2.30&Aring;" />
 '''Crystal Structure of the AHL Synthase LasI'''<br />
 ==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.
+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==
-RO5 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RO5 OCA].
+RO5 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==
@@ Line 13: / Line 13: @@
 [[Category: Pseudomonas aeruginosa]]
 [[Category: Single protein]]
-[[Category: Churchill, M.E.]]
+[[Category: Churchill, M E.]]
-[[Category: Gould, T.A.]]
+[[Category: Gould, T A.]]
-[[Category: Schweizer, H.P.]]
+[[Category: Schweizer, H P.]]
 [[Category: SO4]]
 [[Category: ZN]]
@@ Line 21: / Line 21: @@
 [[Category: phosphopantetheine fold]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:44:50 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:52:54 2008''