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| | <StructureSection load='6p9c' size='340' side='right'caption='[[6p9c]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='6p9c' size='340' side='right'caption='[[6p9c]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6p9c]] is a 2 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=6P9C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P9C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6p9c]] is a 2 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=6P9C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P9C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4J6:(4R,5S)-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-3-({(3S,5S)-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL}SULFANYL)-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>4J6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=O6P:Doripenem'>O6P</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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla OXA-48, blaOXA-48, KPE71T_00045 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4J6:(4R,5S)-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-3-({(3S,5S)-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL}SULFANYL)-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>4J6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=O6P:(4~{R},5~{S},6~{S})-4-methyl-6-[(1~{R})-1-oxidanylethyl]-7-oxidanylidene-3-[(3~{S},5~{S})-5-[(sulfamoylamino)methyl]pyrrolidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic+acid'>O6P</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6p9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p9c OCA], [https://pdbe.org/6p9c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p9c RCSB], [https://www.ebi.ac.uk/pdbsum/6p9c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p9c ProSAT]</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=6p9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p9c OCA], [http://pdbe.org/6p9c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p9c RCSB], [http://www.ebi.ac.uk/pdbsum/6p9c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p9c ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 18: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6p9c" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6p9c" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Klebsiella pneumoniae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Smith, C A]] | + | [[Category: Smith CA]] |
| - | [[Category: Vakulenko, S B]] | + | [[Category: Vakulenko SB]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Carbapenemase]]
| + | |
| - | [[Category: Dorupenem complex]]
| + | |
| - | [[Category: Hydrolase-antibiotic complex]]
| + | |
| Structural highlights
6p9c is a 2 chain structure with sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.9Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q6XEC0_KLEPN
Publication Abstract from PubMed
Carbapenem-hydrolyzing class D carbapenemases (CHDLs) are enzymes that produce resistance to the last resort carbapenem antibiotics, severely compromising available therapeutic options for treatment of life-threatening infections. A broad variety of CHDLs, including OXA-23, OXA-24/40 and OXA-58, circulate in Acinetobacter baumannii, while the OXA-48 CHDL is predominant in Enterobacteriaceae Extensive structural studies of A. baumannii enzymes provided important information regarding their interactions with carbapenems and significantly contributed to the understanding of the mechanism of their carbapenemase activity. However, the interactions between carbapenems and OXA-48 have not yet been elucidated. We determined X-ray crystal structures of the acyl-enzyme complexes of OXA-48 with four carbapenems, imipenem, meropenem, ertapenem and doripenem, and compared them with known carbapenem complexes of A. baumannii CHDLs. In the A. baumannii enzymes, acylation by carbapenems triggers significant displacement of one of two conserved hydrophobic surface residues, resulting in formation of a channel for entry of the deacylating water into the active site. We show that such channel pre-exists in apo-OXA-48 and only minor displacement of the conserved hydrophobic surface residues occurs upon formation of OXA-48 acyl-enzyme intermediates. We also demonstrate that extensive hydrophobic interactions that occur between a conserved hydrophobic bridge of the A. baumannii CHDLs and the carbapenem tails, are lost in OXA-48 in the absence of an equivalent bridge structure. These data highlight significant differences between the interactions of carbapenems with OXA-48 when compared to those with A. baumannii enzymes and provide important insights into the mechanism of carbapenemase activity of the major Enterobacteriaceae CHDL, OXA-48.
Structural Insights into the Mechanism of Carbapenemase Activity of the OXA-48 beta-Lactamase.,Smith CA, Stewart NK, Toth M, Vakulenko SB Antimicrob Agents Chemother. 2019 Jul 29. pii: AAC.01202-19. doi:, 10.1128/AAC.01202-19. PMID:31358584[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Smith CA, Stewart NK, Toth M, Vakulenko SB. Structural Insights into the Mechanism of Carbapenemase Activity of the OXA-48 beta-Lactamase. Antimicrob Agents Chemother. 2019 Jul 29. pii: AAC.01202-19. doi:, 10.1128/AAC.01202-19. PMID:31358584 doi:http://dx.doi.org/10.1128/AAC.01202-19
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