Type

Journal Article

Authors

R L Levine
J Moss
N Wehr
N G McElvaney
G Kim
D Cervantes-Laurean
C Taggart

Subjects

Biochemistry

Topics
mutagenesis site directed molecular structure models molecular genetics alpha 1 antitrypsin mass oxidation reduction antagonists inhibitors methionine humans metabolism spectrometry leukocyte elastase matrix assisted laser recombinant proteins chemistry

Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity. (2000)

Abstract Hydrogen peroxide is a component of cigarette smoke known to be essential for inactivation of alpha(1)-antitrypsin, the primary inhibitor of neutrophil elastase. To establish the molecular basis of the inactivation of alpha(1)-antitrypsin, we determined the sites oxidized by hydrogen peroxide. Two of the nine methionines were particularly susceptible to oxidation. One was methionine 358, whose oxidation was known to cause loss of anti-elastase activity. The other, methionine 351, was as susceptible to oxidation as methionine 358. Its oxidation also resulted in loss of anti-elastase activity, an effect not previously recognized. The equal susceptibility of methionine 358 and methionine 351 to oxidation was confirmed by mass spectrometry. To verify this finding, we produced recombinant alpha(1)-antitrypsins in which one or both of the susceptible methionines were mutated to valine. M351V and M358V were not as rapidly inactivated as wild-type alpha1-antitrypsin, but only the double mutant M351V/M358V was markedly resistant to oxidative inactivation. We suggest that inactivation of alpha(1)-antitrypsin by oxidation of either methionine 351 or 358 provides a mechanism for regulation of its activity at sites of inflammation.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

R L Levine, J Moss, N Wehr, N G McElvaney, G Kim, D Cervantes-Laurean, C Taggart

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54