Deep profiling of protease substrate specificity enabled by dual random and scanned human proteome substrate phage libraries
Jie Zhou, Shantao Li, Kevin Leung, Brian D. O’Donovan, James Zou, Joseph L. DeRisi, James A. Wells
Abstract
natural linear cut sites, depending on the protease, and captured most of the examples previously identified by proteomics and predicted 10- to 100-fold more. Structural bioinformatics was used to facilitate the identification of candidate natural protein substrates. SPD-NGS is rapid, reproducible, simple to perform and analyze, inexpensive, and renewable, with unprecedented depth of coverage for substrate sequences, and is an important tool for protease biologists interested in protease specificity for specific assays and inhibitors and to facilitate identification of natural protein substrates.
Topics & Concepts
ProteasesProteaseSubstrate specificityBiologyProteomeCell biologyCaspaseComputational biologyPhage displayEnzymeBiochemistryGeneticsProgrammed cell deathApoptosisAntibodyBiochemical and Structural CharacterizationMachine Learning in BioinformaticsPeptidase Inhibition and Analysis