Scientific paper recognised as a JBC Classic

The Journal of Biological Chemistry (JBC) recognised one of our scientific papers published in 1985 as a JBC Classic. A link to this announcement can be be seen at http:/www.jbc.org/content/ 292/1/80.full.html.

The actual paper is: “Isolation and Properties of Recombinant DNA Produced Variants of Human alpha-1-Proteinase Inhibitor (= alpha-1-antitrypsin)” by  James Travis, Maurice Owen, Peter George, Robin Carrell, Stephen Rosenberg, Robert Halliwell and Philip Barr and published in the  Journal of  Biological  Chemistry  Vol 260 No 7, 4384-4389, 1985.

This work followed on from an earlier paper by Maurice Owen, Stephen Brennan,  Jessica Lewis and Robin Carrell, “Mutation of antitrypsin to antithrombin. Alpha -1-antitrypsin Pittsburgh (386 Met to Arg), a Fatal Bleeding disorder” published in the New England Journal of Medicine 1983: 309:694-698. This showed how a single change at the active site of antitrypsin dramatically changed the protein from an inhibitor of elastase to an inhibitor of thrombin which resulted in a fatal bleeding disorder.

Professor Jim Travis, from the University of Georgia  USA, spent a few months with us in Christchurch NZ in 1984 where he worked on modifying the active site amino acid of alpha-1-antitrypsin from the native Methionine, which is susceptible to oxidation, to a Valine, which is resistant to oxidation. This resulted in a non-oxidisable form of the protein.  Antitrypsin protects the lungs from emphysema. However it loses its protective activity if it is oxidised – which can occur in subjects that are heavy smokers.

This work was done when recombinant DNA technology was in its infancy. It was one of the first demonstrations of the ability to tailor-make therapeutics.

Published on Monday, March 6th, 2017, under Blog