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| | ==The 1.4 A structure of the class D beta-lactamase OXA-1 K70D complexed with oxacillin== | | ==The 1.4 A structure of the class D beta-lactamase OXA-1 K70D complexed with oxacillin== |
| - | <StructureSection load='4mll' size='340' side='right' caption='[[4mll]], [[Resolution|resolution]] 1.37Å' scene=''> | + | <StructureSection load='4mll' size='340' side='right'caption='[[4mll]], [[Resolution|resolution]] 1.37Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mll]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4f7y 4f7y]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MLL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MLL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mll]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4f7y 4f7y]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MLL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1S6:(2R,4S)-5,5-DIMETHYL-2-[(1R)-1-{[(5-METHYL-3-PHENYL-1,2-OXAZOL-4-YL)CARBONYL]AMINO}-2-OXOETHYL]-1,3-THIAZOLIDINE-4-CARBOXYLIC+ACID'>1S6</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1S6:(2R,4S)-5,5-DIMETHYL-2-[(1R)-1-{[(5-METHYL-3-PHENYL-1,2-OXAZOL-4-YL)CARBONYL]AMINO}-2-OXOETHYL]-1,3-THIAZOLIDINE-4-CARBOXYLIC+ACID'>1S6</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f94|4f94]]</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=4mll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mll OCA], [https://pdbe.org/4mll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mll RCSB], [https://www.ebi.ac.uk/pdbsum/4mll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mll ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, bla oxa1, oxa1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=4mll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mll OCA], [http://pdbe.org/4mll PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mll RCSB], [http://www.ebi.ac.uk/pdbsum/4mll PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mll ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BLO1_ECOLX BLO1_ECOLX]] This is an oxacillin-hydrolyzing beta-lactamase. | + | [https://www.uniprot.org/uniprot/BLO1_ECOLX BLO1_ECOLX] This is an oxacillin-hydrolyzing beta-lactamase. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Beta-lactamase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bonomo, R A]] | + | [[Category: Bonomo RA]] |
| - | [[Category: June, C M]] | + | [[Category: June CM]] |
| - | [[Category: Leonard, D A]] | + | [[Category: Leonard DA]] |
| - | [[Category: Powers, R A]] | + | [[Category: Powers RA]] |
| - | [[Category: Vallier, B C]] | + | [[Category: Vallier BC]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-antibiotic complex]]
| + | |
| - | [[Category: Oxacillinase]]
| + | |
| Structural highlights
Function
BLO1_ECOLX This is an oxacillin-hydrolyzing beta-lactamase.
Publication Abstract from PubMed
Since the discovery and use of penicillin, the increase of antibiotic resistance among bacterial pathogens has become a major health concern. The most prevalent resistance mechanism in Gram-negative bacteria is due to beta-lactamase expression. Class D beta-lactamases are of particular importance due to their presence in multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. The class D enzymes were initially characterized by their ability to efficiently hydrolyze isoxazolyl-type beta-lactams like oxacillin. Due to this substrate preference, these enzymes are traditionally referred to as oxacillinases or OXAs. However, this class is comprised of subfamilies characterized by diverse activities that include oxacillinase, carbapenemase, or cephalosporinase substrate specificity. OXA-1 represents one subtype of class D enzyme that efficiently hydrolyzes oxacillin, and OXA-24/40 represents another with weak oxacillinase, but increased carbapenemase, activity. To examine the structural basis for the substrate selectivity differences between OXA-1 and OXA-24/40, the X-ray crystal structures of deacylation-deficient mutants of these enzymes (Lys70Asp for OXA-1; Lys84Asp for OXA-24) in complexes with oxacillin were determined to 1.4 A and 2.4 A, respectively. In the OXA-24/40/oxacillin structure, the hydrophobic R1 side chain of oxacillin disrupts the bridge between Tyr112 and Met223 present in the apo OXA-24/40 structure, causing the main chain of the Met223-containing loop to adopt a completely different conformation. In contrast, in the OXA-1/oxacillin structure, a hydrophobic pocket consisting of Trp102, Met99, Phe217, Leu161, and Leu255 nicely complements oxacillin's nonpolar R1 side chain. Comparison of the OXA-1/oxacillin and OXA-24/40/oxacillin complexes provides novel insight on how substrate selectivity is achieved among subtypes of class D beta-lactamases. By elucidating important active site interactions, these findings can also inform the design of novel antibiotics and inhibitors.
Structural Origins of Oxacillinase Specificity in Class D beta-Lactamases.,June CM, Vallier BC, Bonomo RA, Leonard DA, Powers RA Antimicrob Agents Chemother. 2014 Jan;58(1):333-41. doi: 10.1128/AAC.01483-13., Epub 2013 Oct 28. PMID:24165180[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ June CM, Vallier BC, Bonomo RA, Leonard DA, Powers RA. Structural Origins of Oxacillinase Specificity in Class D beta-Lactamases. Antimicrob Agents Chemother. 2014 Jan;58(1):333-41. doi: 10.1128/AAC.01483-13., Epub 2013 Oct 28. PMID:24165180 doi:http://dx.doi.org/10.1128/AAC.01483-13
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