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| | ==Crystal structure of NDM-1 at pH5.5 (Bis-Tris) in complex with hydrolyzed ampicillin== | | ==Crystal structure of NDM-1 at pH5.5 (Bis-Tris) in complex with hydrolyzed ampicillin== |
| - | <StructureSection load='5zge' size='340' side='right' caption='[[5zge]], [[Resolution|resolution]] 1.00Å' scene=''> | + | <StructureSection load='5zge' size='340' side='right'caption='[[5zge]], [[Resolution|resolution]] 1.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zge]] 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]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3q6x 3q6x]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZGE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zge]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3q6x 3q6x]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZGE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OH:HYDROXIDE+ION'>OH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=ZZ7:(2R,4S)-2-[(R)-{[(2R)-2-AMINO-2-PHENYLACETYL]AMINO}(CARBOXY)METHYL]-5,5-DIMETHYL-1,3-THIAZOLIDINE-4-CARBOXYLIC+ACID'>ZZ7</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]] 1Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OH:HYDROXIDE+ION'>OH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=ZZ7:(2R,4S)-2-[(R)-{[(2R)-2-AMINO-2-PHENYLACETYL]AMINO}(CARBOXY)METHYL]-5,5-DIMETHYL-1,3-THIAZOLIDINE-4-CARBOXYLIC+ACID'>ZZ7</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=5zge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zge OCA], [https://pdbe.org/5zge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zge RCSB], [https://www.ebi.ac.uk/pdbsum/5zge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zge 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=5zge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zge OCA], [http://pdbe.org/5zge PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zge RCSB], [http://www.ebi.ac.uk/pdbsum/5zge PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zge 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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| | ==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: Hao, Q]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhang, H]] | + | [[Category: Hao Q]] |
| - | [[Category: Antibiotic]] | + | [[Category: Zhang H]] |
| - | [[Category: Antibiotic resistent]]
| + | |
| - | [[Category: Conformational change]]
| + | |
| - | [[Category: Hydrolase-antibiotic complex]]
| + | |
| - | [[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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