L2' loop is critical for caspase-7 active site formation.

ABSTRACT: The active sites of caspases are composed of four mobile loops. A loop (L2) from one half of the dimer interacts with a loop (L2') from the other half of the dimer to bind substrate. In an inactive form, the two L2' loops form a cross-dimer hydrogen-bond network over the dimer interface. Although the L2' loop has been implicated as playing a central role in the formation of the active-site loop bundle, its precise role in catalysis has not been shown. A detailed understanding of the active and inactive conformations is essential to control the caspase function. We have interrogated the contributions of the residues in the L2' loop to catalytic function and enzyme stability. In wild-type and all mutants, active-site binding results in substantial stabilization of the complex. One mutation,

SUBMITTER: Witkowski WA 

PROVIDER: S-EPMC2775214 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature