Key feature of the catalytic cycle of TNF-alpha converting enzyme involves communication between distal protein sites and the enzyme catalytic core.

ABSTRACT: Despite their key roles in many normal and pathological processes, the molecular details by which zinc-dependent proteases hydrolyze their physiological substrates remain elusive. Advanced theoretical analyses have suggested reaction models for which there is limited and controversial experimental evidence. Here we report the structure, chemistry and lifetime of transient metal-protein reaction intermediates evolving during the substrate turnover reaction of a metalloproteinase, the tumor necrosis factor-alpha converting enzyme (TACE). TACE controls multiple signal transduction pathways through the proteolytic release of the extracellular domain of a host of membrane-bound factors and receptors. Using stopped-flow x-ray spectroscopy methods together with transient kinetic analyses, we demo

SUBMITTER: Solomon A 

PROVIDER: S-EPMC1829242 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature