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- Publisher Website: 10.1096/fj.11-184036
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- PMID: 21507902
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Article: Crystal structure of NDM-1 reveals a common β-lactam hydrolysis mechanism
Title | Crystal structure of NDM-1 reveals a common β-lactam hydrolysis mechanism | ||||
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Authors | |||||
Keywords | Ampicillin Antibiotic resistance Inhibitor design New delhi metallo-β-lactamase | ||||
Issue Date | 2011 | ||||
Publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/ | ||||
Citation | Faseb Journal, 2011, v. 25 n. 8, p. 2574-2582 How to Cite? | ||||
Abstract | Metallo-β-lactamases (MBLs) hydrolyze most β-lactam antibiotics, and bacteria containing this kind of enzyme pose a serious threat to the public health. The newly identified New Delhi MBL (NDM-1) is a new member of this family that shows tight binding to penicillin and cephalosporins. The rapid dissemination of NDM-1 in clinically relevant bacteria has become a global concern. However, no clinically useful inhibitors against MBLs exist, partly due to the lack of knowledge about the catalysis mechanism of this kind of enzyme. Here we report the crystal structure of this novel enzyme in complex with a hydrolyzed ampicillin at its active site at 1.3-Å resolution. Structural comparison with other MBLs revealed a new hydrolysis mechanism applicable to all three subclasses of MBLs, which might help the design of mechanism based inhibitors. | ||||
Persistent Identifier | http://hdl.handle.net/10722/135382 | ||||
ISSN | 2023 Impact Factor: 4.4 2023 SCImago Journal Rankings: 1.412 | ||||
ISI Accession Number ID |
Funding Information: This work was supported by Research Grant Council of Hong Kong grants HKU765909M and HKU785110M to Q.H. and H.-M.Z. The crystallographic data were collected at the Shanghai Synchrotron Radiation Facility (Shanghai, China). | ||||
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Zhang, H | en_HK |
dc.contributor.author | Hao, Q | en_HK |
dc.date.accessioned | 2011-07-27T01:34:26Z | - |
dc.date.available | 2011-07-27T01:34:26Z | - |
dc.date.issued | 2011 | en_HK |
dc.identifier.citation | Faseb Journal, 2011, v. 25 n. 8, p. 2574-2582 | en_HK |
dc.identifier.issn | 0892-6638 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/135382 | - |
dc.description.abstract | Metallo-β-lactamases (MBLs) hydrolyze most β-lactam antibiotics, and bacteria containing this kind of enzyme pose a serious threat to the public health. The newly identified New Delhi MBL (NDM-1) is a new member of this family that shows tight binding to penicillin and cephalosporins. The rapid dissemination of NDM-1 in clinically relevant bacteria has become a global concern. However, no clinically useful inhibitors against MBLs exist, partly due to the lack of knowledge about the catalysis mechanism of this kind of enzyme. Here we report the crystal structure of this novel enzyme in complex with a hydrolyzed ampicillin at its active site at 1.3-Å resolution. Structural comparison with other MBLs revealed a new hydrolysis mechanism applicable to all three subclasses of MBLs, which might help the design of mechanism based inhibitors. | en_HK |
dc.language | eng | en_US |
dc.publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/ | en_HK |
dc.relation.ispartof | FASEB Journal | en_HK |
dc.subject | Ampicillin | en_HK |
dc.subject | Antibiotic resistance | en_HK |
dc.subject | Inhibitor design | en_HK |
dc.subject | New delhi metallo-β-lactamase | en_HK |
dc.subject.mesh | Ampicillin - metabolism | - |
dc.subject.mesh | Enterobacteriaceae - drug effects - enzymology - genetics - pathogenicity | - |
dc.subject.mesh | Hydrolysis | - |
dc.subject.mesh | beta-Lactamases - chemistry - genetics - metabolism | - |
dc.subject.mesh | beta-Lactams - metabolism | - |
dc.title | Crystal structure of NDM-1 reveals a common β-lactam hydrolysis mechanism | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Hao, Q: qhao@hku.hk | en_HK |
dc.identifier.authority | Hao, Q=rp01332 | en_HK |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1096/fj.11-184036 | en_HK |
dc.identifier.pmid | 21507902 | - |
dc.identifier.scopus | eid_2-s2.0-79957618735 | en_HK |
dc.identifier.hkuros | 187523 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-79957618735&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 25 | en_HK |
dc.identifier.issue | 8 | en_HK |
dc.identifier.spage | 2574 | en_HK |
dc.identifier.epage | 2582 | en_HK |
dc.identifier.eissn | 1530-6860 | - |
dc.identifier.isi | WOS:000293337800008 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Zhang, H=37035621300 | en_HK |
dc.identifier.scopusauthorid | Hao, Q=7102508868 | en_HK |
dc.identifier.issnl | 0892-6638 | - |