Nature Communications (Aug 2016)

A substrate-driven allosteric switch that enhances PDI catalytic activity

  • Roelof H. Bekendam,
  • Pavan K. Bendapudi,
  • Lin Lin,
  • Partha P. Nag,
  • Jun Pu,
  • Daniel R. Kennedy,
  • Alexandra Feldenzer,
  • Joyce Chiu,
  • Kristina M. Cook,
  • Bruce Furie,
  • Mingdong Huang,
  • Philip J. Hogg,
  • Robert Flaumenhaft

DOI
https://doi.org/10.1038/ncomms12579
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 11

Abstract

Read online

Protein Disulfide Isomerase (PDI) is a prothrombotic, multidomain enzyme with separate substrate binding and catalytic domains. Here, the authors identify a new class of compounds that target the PDI substrate binding site, inducing a conformational change in the catalytic domains and inhibiting thrombosis.