|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of the class A extended-spectrum beta-lactamase CTX- M-96, a natural D240G mutant derived from CTX-M-12== | | ==Crystal structure of the class A extended-spectrum beta-lactamase CTX- M-96, a natural D240G mutant derived from CTX-M-12== |
| - | <StructureSection load='3zny' size='340' side='right' caption='[[3zny]], [[Resolution|resolution]] 1.20Å' scene=''> | + | <StructureSection load='3zny' size='340' side='right'caption='[[3zny]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zny]] 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=3ZNY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZNY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zny]] 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=3ZNY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZNY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3znt|3znt]], [[3znw|3znw]]</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]] 1.2Å</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=3zny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zny OCA], [https://pdbe.org/3zny PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zny RCSB], [https://www.ebi.ac.uk/pdbsum/3zny PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zny 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=3zny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zny OCA], [http://pdbe.org/3zny PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zny RCSB], [http://www.ebi.ac.uk/pdbsum/3zny PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zny ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6ZXB6_KLEPN Q6ZXB6_KLEPN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 19: |
Line 20: |
| | | | |
| | ==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: Bouillenne, F]] | + | [[Category: Large Structures]] |
| - | [[Category: Charlier, P]] | + | [[Category: Bouillenne F]] |
| - | [[Category: Galleni, M]] | + | [[Category: Charlier P]] |
| - | [[Category: Ghiglione, B]] | + | [[Category: Galleni M]] |
| - | [[Category: Gutkind, G]] | + | [[Category: Ghiglione B]] |
| - | [[Category: Herman, R]] | + | [[Category: Gutkind G]] |
| - | [[Category: Power, P]] | + | [[Category: Herman R]] |
| - | [[Category: Rodriguez, M M]] | + | [[Category: Power P]] |
| - | [[Category: Sauvage, E]] | + | [[Category: Rodriguez MM]] |
| - | [[Category: Ceftazidimase]]
| + | [[Category: Sauvage E]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Oxyimino-cephalosporinase]]
| + | |
| Structural highlights
Function
Q6ZXB6_KLEPN
Publication Abstract from PubMed
Diversification of the CTX-M beta-lactamases led to the emergence of variants responsible for decreased susceptibility to ceftazidime, like the Asp240Gly-harboring "ceftazidimases". We solved the crystallographic structure of the Asp240Gly variant CTX-M-96 at 1.2 A and evaluated the role of Asp240 in the activity toward oxyimino-cephalosporins through simulated models and kinetics. There seem to be subtle changes in the conformation of the active site cavity of CTX-M-96, compared to enzyme variants harboring the Asp240, and these small rearrangements could be due to localized shifts in the environment of the beta3 strand. According to the crystallographic evidence, CTX-M-96 presents a "compact" active site, which in spite of its reduced cavity seems to allow the proper interaction with oxyimino-cephalosporins, as suggested by simulated models. The term "ceftazidimases" that is currently applied for the Asp240Gly-harboring CTX-M variants should be used carefully. Structural differences between CTX-M harboring the Asp240Gly mutation (and also probably others like those at Pro167) do not seem to be conclusive to determine the "ceftazidimase" behavior observed in vivo, which is in turn partially supported by the mild improvement in the catalytic efficiency toward ceftazidime by CTX-M-96 and similar enzymes, compared to "parental" Asp240-harboring variants. In addition, it is observed that alterations in OmpF expression could act synergistically with CTX-M-96 for yielding clinical resistance toward ceftazidime. We therefore propose that the observed resistance in vivo is due to the sum of synergic mechanisms, and the term "cefotaximases associated with ceftazidime resistance" could be conveniently used to describe CTX-M harboring the Asp240Gly substitution.
Structural and Kinetic Insights into the "Ceftazidimase" Behavior of the Extended-Spectrum beta-Lactamase CTX-M-96.,Ghiglione B, Rodriguez MM, Herman R, Curto L, Dropa M, Bouillenne F, Kerff F, Galleni M, Charlier P, Gutkind G, Sauvage E, Power P Biochemistry. 2015 Aug 10. PMID:26228623[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ghiglione B, Rodriguez MM, Herman R, Curto L, Dropa M, Bouillenne F, Kerff F, Galleni M, Charlier P, Gutkind G, Sauvage E, Power P. Structural and Kinetic Insights into the "Ceftazidimase" Behavior of the Extended-Spectrum beta-Lactamase CTX-M-96. Biochemistry. 2015 Aug 10. PMID:26228623 doi:http://dx.doi.org/10.1021/acs.biochem.5b00313
|
