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J Med Chem. 2008 Apr 10;51(7):2003-8. doi: 10.1021/jm700966p. Epub 2008 Mar 5.

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

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1
Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.

Abstract

The 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.

PMID:
18318470
PMCID:
PMC3623276
DOI:
10.1021/jm700966p
[Indexed for MEDLINE]
Free PMC Article

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