2aio: Difference between revisions
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<StructureSection load='2aio' size='340' side='right' caption='[[2aio]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='2aio' size='340' side='right' caption='[[2aio]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2aio]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2aio]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"pseudomonas_maltophilia"_hugh_and_ryschenkow_1961 "pseudomonas maltophilia" hugh and ryschenkow 1961]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AIO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AIO FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sml|1sml]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sml|1sml]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=40324 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=40324 "Pseudomonas maltophilia" Hugh and Ryschenkow 1961])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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.rcsb.org/pdb/explore.do?structureId=2aio RCSB], [http://www.ebi.ac.uk/pdbsum/2aio PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/2aio PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aio RCSB], [http://www.ebi.ac.uk/pdbsum/2aio PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/ | [[http://www.uniprot.org/uniprot/BLA1_STEMA BLA1_STEMA]] Has a high activity against imipenem. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2aio" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Pseudomonas maltophilia hugh and ryschenkow 1961]] | |||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Blackburn, G M]] | [[Category: Blackburn, G M]] | ||
[[Category: Gamblin, S J]] | [[Category: Gamblin, S J]] | ||
Revision as of 09:23, 11 September 2015
Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactamMetallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam
Structural highlights
Function[BLA1_STEMA] Has a high activity against imipenem. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMetallo-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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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