2.4 A resolution crystal structure of the prototypical hormone-processing protease Kex2 in complex with an Ala-Lys-Arg boronic acid inhibitor. Academic Article uri icon

Overview

abstract

  • This paper reports the first structure of a member of the Kex2/furin family of eukaryotic pro-protein processing proteases, which cleave sites consisting of pairs or clusters of basic residues. Reported is the 2.4 A resolution crystal structure of the two-domain protein ssKex2 in complex with an Ac-Ala-Lys-boroArg inhibitor (R = 20.9%, R(free) = 24.5%). The Kex2 proteolytic domain is similar in its global fold to the subtilisin-like superfamily of degradative proteases. Analysis of the complex provides a structural basis for the extreme selectivity of this enzyme family that has evolved from a nonspecific subtilisin-like ancestor. The P-domain of ssKex2 has a novel jelly roll like fold consisting of nine beta strands and may potentially be involved, along with the buried Ca(2+) ion, in creating the highly determined binding site for P(1) arginine.

publication date

  • June 10, 2003

Research

keywords

  • Boronic Acids
  • Oligopeptides
  • Proprotein Convertases
  • Protease Inhibitors
  • Saccharomyces cerevisiae Proteins
  • Subtilisins

Identity

Scopus Document Identifier

  • 0037647026

Digital Object Identifier (DOI)

  • 10.1021/bi034434t

PubMed ID

  • 12779325

Additional Document Info

volume

  • 42

issue

  • 22