This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2h6a
From Proteopedia
| Line 11: | Line 11: | ||
'''Crystal structure of the zinc-beta-lactamase L1 from Stenotrophomonas maltophilia (mono zinc form)''' | '''Crystal structure of the zinc-beta-lactamase L1 from Stenotrophomonas maltophilia (mono zinc form)''' | ||
| + | |||
| + | ==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== | ||
2H6A 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=2H6A OCA]. | 2H6A 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=2H6A 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:[http://www.ncbi.nlm.nih.gov/pubmed/17999929 17999929] | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 25: | Line 31: | ||
[[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 12:15:26 2008'' |
Revision as of 09:15, 18 June 2008
Crystal structure of the zinc-beta-lactamase L1 from Stenotrophomonas maltophilia (mono zinc form)
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
2H6A 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 12:15:26 2008
