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X-ray snapshot of the mechanism of inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1-dioxide derivatives

dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorHuang, Weijunen_US
dc.contributor.authorYamamoto, Yasufumien_US
dc.contributor.authorLi, Yien_US
dc.contributor.authorDou, Dengfengen_US
dc.contributor.authorAlliston, Kevin R.en_US
dc.contributor.authorHanzlik, Robert P.en_US
dc.contributor.authorWilliams, Todd D.en_US
dc.contributor.authorGroutas, William C.en_US
dc.date.accessioned2012-02-06T17:16:02Z
dc.date.available2012-02-06T17:16:02Z
dc.date.issued2008-04-10en_US
dc.identifier18318470en_US
dc.identifier9716531en_US
dc.identifierHL 57788/ P20 RR 17708en_US
dc.identifier.citationJournal of medicinal chemistry. 2008 Apr 10; 51(7): 2003-8.en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://dx.doi.org/10.1021/jm700966pen_US
dc.identifier.urihttp://hdl.handle.net/10057/4296
dc.descriptionClick on the DOI link below to access the article (may not be free).en_US
dc.description.abstractThe mechanism of action of a general class of mechanism-based inhibitors of serine proteases, including human neutrophil elastase (HNE), has been elucidated by determining the X-ray crystal structure of an enzyme-inhibitor complex. The captured intermediate indicates that processing of inhibitor by the enzyme generates an N-sulfonyl imine functionality that is tethered to Ser195, in accordance with the postulated mechanism of action of this class of inhibitors. The identity of the HNE-N-sulfonyl imine species was further corroborated using electrospray ionization mass spectrometry.en_US
dc.description.sponsorshipNHLBI NIH HHS/ NCRR NIH HHSen_US
dc.format.extent2003-8en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofseriesJournal of medicinal chemistryen_US
dc.relation.ispartofseriesJ. Med. Chem.en_US
dc.sourceNLMen_US
dc.subjectResearch Support, N.I.H., Extramuralen_US
dc.subjectResearch Support, Non-U.S. Gov'ten_US
dc.subjectResearch Support, U.S. Gov't, Non-P.H.S.en_US
dc.subject.meshBinding Sites/drug effectsen_US
dc.subject.meshCrystallography, X-Rayen_US
dc.subject.meshCyclic S-Oxides/chemical synthesisen_US
dc.subject.meshEnzyme Activation/drug effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshLeukocyte Elastase/antagonists & inhibitorsen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMolecular Structureen_US
dc.subject.meshProtein Structure, Tertiaryen_US
dc.subject.meshSerine Proteinase Inhibitors/chemical synthesisen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshThiazoles/chemical synthesisen_US
dc.subject.meshCyclic S-Oxides/chemistryen_US
dc.subject.meshCyclic S-Oxides/pharmacologyen_US
dc.subject.meshLeukocyte Elastase/chemistryen_US
dc.subject.meshSerine Proteinase Inhibitors/pharmacologyen_US
dc.subject.meshSerine Proteinase Inhibitors/chemistryen_US
dc.subject.meshThiazoles/chemistryen_US
dc.subject.meshThiazoles/pharmacologyen_US
dc.titleX-ray snapshot of the mechanism of inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1-dioxide derivativesen_US
dc.typeArticleen_US
dc.coverage.spacialUnited Statesen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 2008 American Chemical Societyen_US


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