2aio
From Proteopedia
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|PDB= 2aio |SIZE=350|CAPTION= <scene name='initialview01'>2aio</scene>, resolution 1.70Å | |PDB= 2aio |SIZE=350|CAPTION= <scene name='initialview01'>2aio</scene>, resolution 1.70Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= blaL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=40324 Stenotrophomonas maltophilia]) | |GENE= blaL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=40324 Stenotrophomonas maltophilia]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1sml|1sml]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aio OCA], [http://www.ebi.ac.uk/pdbsum/2aio PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2aio RCSB]</span> | ||
}} | }} | ||
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[[Category: Sessions, R B.]] | [[Category: Sessions, R B.]] | ||
[[Category: Spencer, J.]] | [[Category: Spencer, J.]] | ||
| - | [[Category: MX1]] | ||
| - | [[Category: SO4]] | ||
| - | [[Category: ZN]] | ||
[[Category: alpha-beta/beta-alpha fold]] | [[Category: alpha-beta/beta-alpha fold]] | ||
[[Category: binuclear]] | [[Category: binuclear]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:53:18 2008'' |
Revision as of 22:53, 30 March 2008
| |||||||
| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | blaL1 (Stenotrophomonas maltophilia) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Related: | 1sml
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Mon Mar 31 01:53:18 2008
