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| | ==Structure of SHV-1 beta-lactamase in complex with the 7-alkylidenecephalosporin DCM-1-10 at 1.14 Ang resolution== | | ==Structure of SHV-1 beta-lactamase in complex with the 7-alkylidenecephalosporin DCM-1-10 at 1.14 Ang resolution== |
| - | <StructureSection load='4jpm' size='340' side='right' caption='[[4jpm]], [[Resolution|resolution]] 1.14Å' scene=''> | + | <StructureSection load='4jpm' size='340' side='right'caption='[[4jpm]], [[Resolution|resolution]] 1.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jpm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JPM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jpm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JPM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1OG:7-ALKYLIDENECEPHALOSPORIN+DCM-1-10,+BOUND+FORM'>1OG</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1OG:7-ALKYLIDENECEPHALOSPORIN+DCM-1-10,+BOUND+FORM'>1OG</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fh4|4fh4]]</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=4jpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jpm OCA], [https://pdbe.org/4jpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jpm RCSB], [https://www.ebi.ac.uk/pdbsum/4jpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jpm ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, shv1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</td></tr>
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| - | <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>
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| - | <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=4jpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jpm OCA], [http://pdbe.org/4jpm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jpm RCSB], [http://www.ebi.ac.uk/pdbsum/4jpm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jpm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BLA1_KLEPN BLA1_KLEPN] |
| | <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: Beta-lactamase]] | + | [[Category: Klebsiella pneumoniae]] |
| - | [[Category: Akker, F van den]] | + | [[Category: Large Structures]] |
| - | [[Category: Rodkey, E A]] | + | [[Category: Rodkey EA]] |
| - | [[Category: Class a beta-lactamase]] | + | [[Category: Van den Akker F]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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| Structural highlights
Function
BLA1_KLEPN
Publication Abstract from PubMed
The inhibition of the class A SHV-1 beta-lactamase by 7-(tert-butoxycarbonyl)methylidenecephalosporin sulfone was examined kinetically, spectroscopically, and crystallographically. An 1.14A X-ray crystal structure shows that the stable acyl-enzyme, which incorporates an eight-membered ring, is a covalent derivative of Ser70 linked to the 7-carboxy group of 2-H-5,8-dihydro-1,1-dioxo-1,5-thiazocine-4,7-dicarboxylic acid. A cephalosporin-derived enzyme complex of this type is unprecedented and the rearrangement leading to its formation may offer new possibilities for inhibitor design. The observed acyl-enzyme derives its stability from the resonance stabilization conveyed by the -aminoacrylate (i.e. vinylogous urethane) functionality as there is relatively little interaction of the eight-membered ring with active site residues. Two mechanistic schemes are proposed, differing in whether, subsequent to acylation of the active site serine and opening of the beta-lactam, the resultant dihydrothiazine fragments on its own, or is assisted by an adjacent nucleophilic atom, in the form of the carbonyl oxygen of the C7 tert-butyloxycarbonyl group. This compound was also found to be a submicromolar inhibitor of the class C ADC-7 and PDC-3 beta-lactamases.
beta-Lactamase Inhibition by 7-Alkylidenecephalosporin Sulfones: Allylic Transposition and Formation of an Unprecedented Stabilized Acyl-Enzyme.,Rodkey EA, McLeod DC, Bethel CR, Smith KM, Xu Y, Chai W, Che T, Carey PR, Bonomo RA, van den Akker F, Buynak JD J Am Chem Soc. 2013 Nov 12. PMID:24219313[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rodkey EA, McLeod DC, Bethel CR, Smith KM, Xu Y, Chai W, Che T, Carey PR, Bonomo RA, van den Akker F, Buynak JD. beta-Lactamase Inhibition by 7-Alkylidenecephalosporin Sulfones: Allylic Transposition and Formation of an Unprecedented Stabilized Acyl-Enzyme. J Am Chem Soc. 2013 Nov 12. PMID:24219313 doi:http://dx.doi.org/10.1021/ja403598g
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