title: Characterization of noncompetitive regulators of proteasome activity.
abstract: The success of bortezomib, a competitive proteasome inhibitor and a drug approved to treat multiple myeloma, spurred interest in compounds targeting catalytic sites of the enzyme. The aim of this chapter, however, is to focus attention on the small molecule, natural or synthetic compounds binding far away from the catalytic centers, yet modifying the performance of the proteasome. Defining allostery broadly as any kind of ligand-induced, long-distance transfer of conformational signals within a molecule, most such compounds are allosteric effectors capable of regulating the proteasome in vitro and in vivo in a manner more diverse and precise than competitive inhibitors. Proline- and arginine-rich peptides (PR peptides) are examples of such compounds and are currently being considered as potential drugs with anti-inflammatory and proangiogenic activities. This chapter describes a set of methods useful for characterizing the effects of such inhibitors on the proteasome.
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Gaczynska
authors.forename: Pawel A
authors.initials: PA
authors.lastname: Osmulski
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive; D006801:Humans; D007700:Kinetics; D008024:Ligands; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D012441:Saccharomyces cerevisiae / Q000201:enzymology
chemical_list: D008024:Ligands; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex