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| | ==Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam== | | ==Metallo beta lactamase L1 from Stenotrophomonas maltophilia complexed with hydrolyzed moxalactam== |
| - | <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/"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> | + | <table><tr><td colspan='2'>[[2aio]] is a 1 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sml|1sml]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2aio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aio OCA], [https://pdbe.org/2aio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aio RCSB], [https://www.ebi.ac.uk/pdbsum/2aio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aio ProSAT]</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://pdbe.org/2aio PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aio RCSB], [http://www.ebi.ac.uk/pdbsum/2aio PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2aio ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BLA1_STEMA BLA1_STEMA]] Has a high activity against imipenem. | + | [https://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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| | ==See Also== | | ==See Also== |
| - | *[[Beta-lactamase|Beta-lactamase]] | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pseudomonas maltophilia hugh and ryschenkow 1961]] | + | [[Category: Large Structures]] |
| - | [[Category: Beta-lactamase]] | + | [[Category: Stenotrophomonas maltophilia]] |
| - | [[Category: Blackburn, G M]] | + | [[Category: Blackburn GM]] |
| - | [[Category: Gamblin, S J]] | + | [[Category: Gamblin SJ]] |
| - | [[Category: Howell, S]] | + | [[Category: Howell S]] |
| - | [[Category: Read, J]] | + | [[Category: Read J]] |
| - | [[Category: Sessions, R B]] | + | [[Category: Sessions RB]] |
| - | [[Category: Spencer, J]] | + | [[Category: Spencer J]] |
| - | [[Category: Alpha-beta/beta-alpha fold]]
| + | |
| - | [[Category: Binuclear]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metallo-beta-lactamase]]
| + | |
| 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 PubMed
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.
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 Also
References
- ↑ Spencer J, Read J, Sessions RB, Howell S, Blackburn GM, Gamblin SJ. Antibiotic recognition by binuclear metallo-beta-lactamases revealed by X-ray crystallography. J Am Chem Soc. 2005 Oct 19;127(41):14439-44. PMID:16218639 doi:10.1021/ja0536062
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