2btn

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==Overview==
==Overview==
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In many Gram-negative bacteria, including a number of pathogens such as, Pseudomonas aeruginosa and Erwinia carotovora, virulence factor production, and biofilm formation are linked to the quorum-sensing systems that use, diffusible N-acyl-L-homoserine lactones (AHLs) as intercellular messenger, molecules. A number of organisms also contain genes coding for lactonases, that hydrolyze AHLs into inactive products, thereby blocking the, quorum-sensing systems. Consequently, these enzymes attract intense, interest for the development of antiinfection therapies. However, the, catalytic mechanism of AHL-lactonase is poorly understood and subject to, controversy. We here report a 2.0-angstroms resolution structure of the, AHL-lactonase from Bacillus thuringiensis and a 1.7-angstroms crystal, structure of its complex with L-homoserine lactone. Despite limited, sequence similarity, the enzyme shows remarkable structural similarities, to glyoxalase II and RNase Z proteins, members of the, metallo-beta-lactamase superfamily. We present experimental evidence that, AHL-lactonase is a metalloenzyme containing two zinc ions involved in, catalysis, and we propose a catalytic mechanism for bacterial, metallo-AHL-lactonases.
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In many Gram-negative bacteria, including a number of pathogens such as Pseudomonas aeruginosa and Erwinia carotovora, virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusible N-acyl-L-homoserine lactones (AHLs) as intercellular messenger molecules. A number of organisms also contain genes coding for lactonases that hydrolyze AHLs into inactive products, thereby blocking the quorum-sensing systems. Consequently, these enzymes attract intense interest for the development of antiinfection therapies. However, the catalytic mechanism of AHL-lactonase is poorly understood and subject to controversy. We here report a 2.0-angstroms resolution structure of the AHL-lactonase from Bacillus thuringiensis and a 1.7-angstroms crystal structure of its complex with L-homoserine lactone. Despite limited sequence similarity, the enzyme shows remarkable structural similarities to glyoxalase II and RNase Z proteins, members of the metallo-beta-lactamase superfamily. We present experimental evidence that AHL-lactonase is a metalloenzyme containing two zinc ions involved in catalysis, and we propose a catalytic mechanism for bacterial metallo-AHL-lactonases.
==About this Structure==
==About this Structure==
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[[Category: Bacillus thuringiensis]]
[[Category: Bacillus thuringiensis]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Choi, W.C.]]
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[[Category: Choi, W C.]]
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[[Category: Derewenda, Z.S.]]
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[[Category: Derewenda, Z S.]]
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[[Category: Kang, B.S.]]
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[[Category: Kang, B S.]]
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[[Category: Kang, H.O.]]
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[[Category: Kang, H O.]]
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[[Category: Kim, K.J.]]
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[[Category: Kim, K J.]]
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[[Category: Kim, M.H.]]
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[[Category: Kim, M H.]]
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[[Category: Lee, C.H.]]
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[[Category: Lee, C H.]]
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[[Category: Lee, J.K.]]
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[[Category: Lee, J K.]]
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[[Category: Lee, J.S.]]
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[[Category: Lee, J S.]]
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[[Category: Oh, T.K.]]
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[[Category: Oh, T K.]]
[[Category: GOL]]
[[Category: GOL]]
[[Category: ZN]]
[[Category: ZN]]
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[[Category: quorum sensing]]
[[Category: quorum sensing]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:27:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:41:30 2008''

Revision as of 14:41, 21 February 2008


2btn, resolution 2.00Å

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CRYSTAL STRUCTURE AND CATALYTIC MECHANISM OF THE QUORUM-QUENCHING N-ACYL HOMOSERINE LACTONE HYDROLASE

Overview

In many Gram-negative bacteria, including a number of pathogens such as Pseudomonas aeruginosa and Erwinia carotovora, virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusible N-acyl-L-homoserine lactones (AHLs) as intercellular messenger molecules. A number of organisms also contain genes coding for lactonases that hydrolyze AHLs into inactive products, thereby blocking the quorum-sensing systems. Consequently, these enzymes attract intense interest for the development of antiinfection therapies. However, the catalytic mechanism of AHL-lactonase is poorly understood and subject to controversy. We here report a 2.0-angstroms resolution structure of the AHL-lactonase from Bacillus thuringiensis and a 1.7-angstroms crystal structure of its complex with L-homoserine lactone. Despite limited sequence similarity, the enzyme shows remarkable structural similarities to glyoxalase II and RNase Z proteins, members of the metallo-beta-lactamase superfamily. We present experimental evidence that AHL-lactonase is a metalloenzyme containing two zinc ions involved in catalysis, and we propose a catalytic mechanism for bacterial metallo-AHL-lactonases.

About this Structure

2BTN is a Single protein structure of sequence from Bacillus thuringiensis with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase., Kim MH, Choi WC, Kang HO, Lee JS, Kang BS, Kim KJ, Derewenda ZS, Oh TK, Lee CH, Lee JK, Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17606-11. Epub 2005 Nov 28. PMID:16314577

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