cis-dichlorodiammineplatinum (II) as a selective modifier of the oxidation-sensitive reactive-center methionine in alpha 1-antitrypsin.

Journal Article (Journal Article)

Methionine 358 in the plasma protein alpha 1-antitrypsin (alpha 1AT) is an oxidation-sensitive reactive-center residue critical for proteinase-inhibitory activity. Reaction of alpha 1AT with 20 microM to 1.67 mM cis-dichlorodiammineplatinum (II) (cis-DDP) or trans-DDP afforded concentration-dependent loss of trypsin-inhibitory activity. This effect, studied by gel electrophoresis and activity assays, is essentially independent of pH over the range 4.9-8.6. Binding assays showed covalent incorporation of 1 mol of cis-DDP into each mol of alpha 1AT. cis-DDP protected a single methionine residue from oxidation and made alpha 1AT resistant to degradation by papain, which cleaves alpha 1AT at Met358. These findings strongly suggest that cis-DDP inactivates alpha 1AT by binding exclusively to its reactive-center methionine. alpha 1AT bound twice as much platinum when reacted with trans-DDP. Because carboxamidomethylated alpha 1AT incorporated nearly 1 mol of both cis- and trans-DDP, the trans isomer apparently binds to both the reactive-center methionine and to the single cysteine residue of alpha 1AT. Because of its greater selectivity, cis-DDP is the superior reagent for modification of the alpha 1AT reactive-center methionine.

Full Text

Duke Authors

Cited Authors

  • Gonias, SL; Swaim, MW; Massey, MF; Pizzo, SV

Published Date

  • January 5, 1988

Published In

Volume / Issue

  • 263 / 1

Start / End Page

  • 393 - 397

PubMed ID

  • 3257210

International Standard Serial Number (ISSN)

  • 0021-9258


  • eng

Conference Location

  • United States