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Article: Crystal structure of NDM-1 reveals a common β-lactam hydrolysis mechanism

TitleCrystal structure of NDM-1 reveals a common β-lactam hydrolysis mechanism
Authors
KeywordsAmpicillin
Antibiotic resistance
Inhibitor design
New delhi metallo-β-lactamase
Issue Date2011
PublisherFederation 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?
AbstractMetallo-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 Identifierhttp://hdl.handle.net/10722/135382
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong KongHKU765909M
HKU785110M
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 FieldValueLanguage
dc.contributor.authorZhang, Hen_HK
dc.contributor.authorHao, Qen_HK
dc.date.accessioned2011-07-27T01:34:26Z-
dc.date.available2011-07-27T01:34:26Z-
dc.date.issued2011en_HK
dc.identifier.citationFaseb Journal, 2011, v. 25 n. 8, p. 2574-2582en_HK
dc.identifier.issn0892-6638en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135382-
dc.description.abstractMetallo-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.languageengen_US
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/en_HK
dc.relation.ispartofFASEB Journalen_HK
dc.subjectAmpicillinen_HK
dc.subjectAntibiotic resistanceen_HK
dc.subjectInhibitor designen_HK
dc.subjectNew delhi metallo-β-lactamaseen_HK
dc.subject.meshAmpicillin - metabolism-
dc.subject.meshEnterobacteriaceae - drug effects - enzymology - genetics - pathogenicity-
dc.subject.meshHydrolysis-
dc.subject.meshbeta-Lactamases - chemistry - genetics - metabolism-
dc.subject.meshbeta-Lactams - metabolism-
dc.titleCrystal structure of NDM-1 reveals a common β-lactam hydrolysis mechanismen_HK
dc.typeArticleen_HK
dc.identifier.emailHao, Q: qhao@hku.hken_HK
dc.identifier.authorityHao, Q=rp01332en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1096/fj.11-184036en_HK
dc.identifier.pmid21507902-
dc.identifier.scopuseid_2-s2.0-79957618735en_HK
dc.identifier.hkuros187523en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79957618735&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue8en_HK
dc.identifier.spage2574en_HK
dc.identifier.epage2582en_HK
dc.identifier.eissn1530-6860-
dc.identifier.isiWOS:000293337800008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhang, H=37035621300en_HK
dc.identifier.scopusauthoridHao, Q=7102508868en_HK

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