2aio
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2aio.gif|left|200px]] | [[Image:2aio.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2aio", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_2aio| PDB=2aio | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam''' | '''Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam''' | ||
| Line 32: | Line 29: | ||
[[Category: Sessions, R B.]] | [[Category: Sessions, R B.]] | ||
[[Category: Spencer, J.]] | [[Category: Spencer, J.]] | ||
| - | [[Category: | + | [[Category: Alpha-beta/beta-alpha fold]] |
| - | [[Category: | + | [[Category: Binuclear]] |
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Metallo-beta-lactamase]] |
| - | [[Category: | + | [[Category: Zinc]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:05:55 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 16:05, 3 May 2008
Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam
Overview
Metallo-beta-lactamases are zinc-dependent enzymes responsible for resistance to beta-lactam antibiotics in a variety of host bacteria, usually Gram-negative species that act as opportunist pathogens. They hydrolyze all classes of beta-lactam antibiotics, including carbapenems, and escape the action of available beta-lactamase inhibitors. Efforts to develop effective inhibitors have been hampered by the lack of structural information regarding how these enzymes recognize and turn over beta-lactam substrates. We report here the crystal structure of the Stenotrophomonas maltophilia L1 enzyme in complex with the hydrolysis product of the 7alpha-methoxyoxacephem, moxalactam. The on-enzyme complex is a 3'-exo-methylene species generated by elimination of the 1-methyltetrazolyl-5-thiolate anion from the 3'-methyl group. Moxalactam binding to L1 involves direct interaction of the two active site zinc ions with the beta-lactam amide and C4 carboxylate, groups that are common to all beta-lactam substrates. The 7beta-[(4-hydroxyphenyl)malonyl]-amino substituent makes limited hydrophobic and hydrogen bonding contacts with the active site groove. The mode of binding provides strong evidence that a water molecule situated between the two metal ions is the most likely nucleophile in the hydrolytic reaction. These data suggest a reaction mechanism for metallo-beta-lactamases in which both metal ions contribute to catalysis by activating the bridging water/hydroxide nucleophile, polarizing the substrate amide bond for attack and stabilizing anionic nitrogen intermediates. The structure illustrates how a binuclear zinc site confers upon metallo-beta-lactamases the ability both to recognize and efficiently hydrolyze a wide variety of beta-lactam substrates.
About this Structure
2AIO is a Single protein structure of sequence from Stenotrophomonas maltophilia. Full crystallographic information is available from OCA.
Reference
Antibiotic recognition by binuclear metallo-beta-lactamases revealed by X-ray crystallography., Spencer J, Read J, Sessions RB, Howell S, Blackburn GM, Gamblin SJ, J Am Chem Soc. 2005 Oct 19;127(41):14439-44. PMID:16218639 Page seeded by OCA on Sat May 3 19:05:55 2008
