2hb9
From Proteopedia
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'''Crystal Structure of the Zinc-Beta-Lactamase L1 from Stenotrophomonas Maltophilia (Inhibitor 3)''' | '''Crystal Structure of the Zinc-Beta-Lactamase L1 from Stenotrophomonas Maltophilia (Inhibitor 3)''' | ||
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| + | ==Overview== | ||
| + | One mechanism by which bacteria can escape the action of beta-lactam antibiotics is the production of metallo-beta-lactamases. Inhibition of these enzymes should restore the action of these widely used antibiotics. The tetrameric enzyme L1 from Stenotrophomonas maltophilia was used as a model system to determine a series of high-resolution crystal structures of apo, mono and bi-metal substituted proteins as well as protein-inhibitor complexes. Unexpectedly, although the apo structure revealed only few significant structural differences from the holo structure, some inhibitors were shown to induce amino acid side-chain rotations in the tightly packed active site. Moreover, one inhibitor employs a new binding mode in order to interact with the di-zinc center. This structural information could prove essential in the process of elucidation of the mode of interaction between a putative lead compound and metallo-beta-lactamases, one of the main steps in structure-based drug design. | ||
==About this Structure== | ==About this Structure== | ||
2HB9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Stenotrophomonas_maltophilia Stenotrophomonas maltophilia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HB9 OCA]. | 2HB9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Stenotrophomonas_maltophilia Stenotrophomonas maltophilia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HB9 OCA]. | ||
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| + | ==Reference== | ||
| + | Structural insights into the design of inhibitors for the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia., Nauton L, Kahn R, Garau G, Hernandez JF, Dideberg O, J Mol Biol. 2008 Jan 4;375(1):257-69. Epub 2007 Oct 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17999929 17999929] | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Metallo]] | [[Category: Metallo]] | ||
[[Category: Zn]] | [[Category: Zn]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 18 12:15:18 2008'' |
Revision as of 09:15, 18 June 2008
Crystal Structure of the Zinc-Beta-Lactamase L1 from Stenotrophomonas Maltophilia (Inhibitor 3)
Overview
One mechanism by which bacteria can escape the action of beta-lactam antibiotics is the production of metallo-beta-lactamases. Inhibition of these enzymes should restore the action of these widely used antibiotics. The tetrameric enzyme L1 from Stenotrophomonas maltophilia was used as a model system to determine a series of high-resolution crystal structures of apo, mono and bi-metal substituted proteins as well as protein-inhibitor complexes. Unexpectedly, although the apo structure revealed only few significant structural differences from the holo structure, some inhibitors were shown to induce amino acid side-chain rotations in the tightly packed active site. Moreover, one inhibitor employs a new binding mode in order to interact with the di-zinc center. This structural information could prove essential in the process of elucidation of the mode of interaction between a putative lead compound and metallo-beta-lactamases, one of the main steps in structure-based drug design.
About this Structure
2HB9 is a Single protein structure of sequence from Stenotrophomonas maltophilia. Full crystallographic information is available from OCA.
Reference
Structural insights into the design of inhibitors for the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia., Nauton L, Kahn R, Garau G, Hernandez JF, Dideberg O, J Mol Biol. 2008 Jan 4;375(1):257-69. Epub 2007 Oct 22. PMID:17999929 Page seeded by OCA on Wed Jun 18 12:15:18 2008
