Differential P1 arginine and lysine recognition in the prototypical proprotein convertase Kex2.

ABSTRACT: The high-resolution crystal structure of kexin (Kex2) in complex with a peptidyl-chloromethylketone inhibitor containing a noncognate lysine at the P(1) position provides the structural basis for the differential lysine/arginine selectivity that defines the prohormone (proprotein) convertase (PC) family. By comparison with the previous structures of Kex2 and furin, this structure of the acylated enzyme provides a basis for the observed decrease in the acylation rate with substrates containing a lysine at P(1) and the absence of an effect on the deacylation rate without involving mobility of the S(1) lid. The structure of the complex shows that a secondary subsite in the S(1) pocket is present, and that this site recognizes and binds the P(1) lysine in a more shallow fashion than arginine.

SUBMITTER: Wheatley JL 

PROVIDER: S-EPMC1871836 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature