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| | ==Crystal structure of NDM-1 at pH7.5 with 1 molecule per asymmetric unit (crystallized at succinate pH5.5 and soaked at succinate pH7.5)== | | ==Crystal structure of NDM-1 at pH7.5 with 1 molecule per asymmetric unit (crystallized at succinate pH5.5 and soaked at succinate pH7.5)== |
| - | <StructureSection load='5zgw' size='340' side='right' caption='[[5zgw]], [[Resolution|resolution]] 0.95Å' scene=''> | + | <StructureSection load='5zgw' size='340' side='right'caption='[[5zgw]], [[Resolution|resolution]] 0.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zgw]] 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=5ZGW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZGW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zgw]] 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=5ZGW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZGW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</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]] 0.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5xp6|5xp6]], [[5zgi|5zgi]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</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">blaNDM-1 ([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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zgw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zgw OCA], [https://pdbe.org/5zgw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zgw RCSB], [https://www.ebi.ac.uk/pdbsum/5zgw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zgw 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=5zgw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zgw OCA], [http://pdbe.org/5zgw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zgw RCSB], [http://www.ebi.ac.uk/pdbsum/5zgw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zgw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN]] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. | + | [https://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5zgw" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5zgw" 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: Hao, Q]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhang, H]] | + | [[Category: Hao Q]] |
| - | [[Category: Antibiotic resistent]] | + | [[Category: Zhang H]] |
| - | [[Category: Conformational change]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metallo-beta-lactamase]]
| + | |
| - | [[Category: Ndm-1]]
| + | |
| Structural highlights
Function
BLAN1_KLEPN Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin.
Publication Abstract from PubMed
Beta-lactam antibiotics are the mainstay for the treatment of bacterial infections. However, elevated resistance to these antibiotics mediated by metallo-beta-lactamases (MBL) has become a global concern. New Delhi metallo-beta-lactamase-1 (NDM-1), a newly added member of the MBL family that can hydrolyze almost all beta-lactam antibiotics, has rapidly spread all over the world and posed serious clinical threats. Broad-spectrum and mechanism-based inhibitors against all MBLs are highly desired, but the differential mechanisms of MBLs towards different antibiotics pose a great challenge. To facilitate the design of mechanism-based inhibitors, we investigated the active-site conformational changes of NDM-1 through the determination of a series of 15 high-resolution crystal structures in native form and in complex with products, biochemical and biophysical studies, site-directed mutagenesis and molecular dynamics computation. The structural studies reveal the consistency of the active site conformations in NDM-1/products complexes and the fluctuation in native NDM-1 structures. The enzymatic measurements indicate a correlation between enzymatic activity and the active site fluctuation with more fluctuation favoring higher activity. This correlation is further validated by structural and enzymatic studies of the Q123G mutant. Our combinational studies suggest that active site conformational fluctuation promotes the enzymatic activity of NDM-1, which may guide further mechanism studies and inhibitor design.
Active site conformational fluctuations promote the enzymatic activity of NDM-1.,Zhang H, Ma G, Zhu Y, Zeng L, Ahmad A, Wang C, Pang B, Fang H, Zhao L, Hao Q Antimicrob Agents Chemother. 2018 Aug 27. pii: AAC.01579-18. doi:, 10.1128/AAC.01579-18. PMID:30150473[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang H, Ma G, Zhu Y, Zeng L, Ahmad A, Wang C, Pang B, Fang H, Zhao L, Hao Q. Active site conformational fluctuations promote the enzymatic activity of NDM-1. Antimicrob Agents Chemother. 2018 Aug 27. pii: AAC.01579-18. doi:, 10.1128/AAC.01579-18. PMID:30150473 doi:http://dx.doi.org/10.1128/AAC.01579-18
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