2aio: Difference between revisions
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[[Image:2aio.gif|left|200px]] | [[Image:2aio.gif|left|200px]] | ||
'''Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam''' | {{Structure | ||
|PDB= 2aio |SIZE=350|CAPTION= <scene name='initialview01'>2aio</scene>, resolution 1.70Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=MX1:(2R)-2-((R)-CARBOXY{[CARBOXY(4-HYDROXYPHENYL)ACETYL]AMINO}METHOXYMETHYL)-5-METHYLENE-5,6-DIHYDRO-2H-1,3-OXAZINE-4-CARBOXYLIC ACID'>MX1</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] | |||
|GENE= blaL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=40324 Stenotrophomonas maltophilia]) | |||
}} | |||
'''Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2AIO is a [ | 2AIO 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=2AIO OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16218639 16218639] | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:50:09 2008'' | ||
Revision as of 16:50, 20 March 2008
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| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | blaL1 (Stenotrophomonas maltophilia) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam
OverviewOverview
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 StructureAbout this Structure
2AIO is a Single protein structure of sequence from Stenotrophomonas maltophilia. Full crystallographic information is available from OCA.
ReferenceReference
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
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