The human peptidase clan CE is defined by seven proteases with a common fold and catalytic mechanism, commonly known as SENPs (sentrin specific proteases - sentrin being an alternative name for SUMO). Current information suggests that most SENPs are specific for processing of SUMO precursors and removing SUMO conjugated to protein substrates. Small-molecule compounds that target SENPs in a selective manner will provide an important toolset to study the biology of these enzymes, to aid in the discovery of their role in disease etiology and progression, and to facilitate the subsequent development of therapeutics against disease-relevant targets. The availability of simple kinetic assays that are applicable the SENPs would significantly enhance the discovery of chemical probes for members of the family, and for .orphan. SENPs with lesser known natural substrate specificity. Our application squarely addresses this ? important unmet need for a development of high-throughput substrate-based assays. We propose to develop small peptide based substrates with broad specificity for all seven human members of the SENP family, and generate simple assay procedures. The assays are expected to provide a tool for the rapid development of chemical probes for members of the family. ? ? ?
| Békés, Miklós; Prudden, John; Srikumar, Tharan et al. (2011) The dynamics and mechanism of SUMO chain deconjugation by SUMO-specific proteases. J Biol Chem 286:10238-47 |
| Drag, Marcin; Salvesen, Guy S (2010) Emerging principles in protease-based drug discovery. Nat Rev Drug Discov 9:690-701 |
