Enzymology at the Membrane Interface: Intramembrane Proteases

Michael H. Gelb studied chemistry and biochemistry as an undergraduate at the University of California at Davis. His Ph.D. studies with Stephen G. Sligar at Yale University led to a better understanding of the catalytic mechanism of cytochrome P450. As an American Cancer Society Postdoctoral Fellow in the laboratory of the late Robert H. Abeles at Brandeis University, Gelb studied a variety of mechanism-based inactivators of serine proteases and developed fluorinated ketones as tight-binding inhibitors of several classes of proteases. In 1985 Gelb became a faculty member in the Departments of Chemistry and Biochemistry at the University of Washington. Major breakthroughs in the group include the development of methods to properly analyze the action of enzymes on membrane surfaces, the discovery of protein prenylation (farnesylation and geranylgeranylation) in mammalian cells (together with John A. Glomset), the development of Isotope-Coded Affinity Tags (ICAT reagents) for proteomic applications (together with Ruedi Aebersold), and the development of newborn screening for lysosomal storage diseases by mass spectrometry.

• 1. Biochemical Characterization of Function and Structure of RseP, an Escherichia Coli S2P ProteaseY. Hizukuri, K. Akiyama and Y. Akiyama2. Signal Peptidase Enzymology and Substrate Specificity ProfilingR.E. Dalbey, D. Pei and Ö.D. Ekici3. Screening and Characterization Strategies for Nanobodies Targeting Membrane ProteinsS. Veugelen, M. Dewilde, B.D. Strooper and L. Chávez-Gutiérrez4. Probing the Activity of Eukaryotic Rhomboid Proteases in VitroB. Cordier and M.K. Lemberg5. Expression, Purification, and Enzymatic Characterization of Intramembrane ProteasesR. Zhou, Y. Shi and G. Yang6. Analyzing Amyloid-β Peptide Modulation Profiles and Binding Sites of γ-Secretase ModulatorsJ. Trambauer, A. Fukumori, B. Kretner and H. Steiner7. Probing the Structure and Function Relationships of Presenilin by Substituted-Cysteine Accessibility MethodT. Tomita8. A New Method to Determine the Transmembrane Conformation of Substrates in Intramembrane Proteolysis by Deep-UV Resonance Raman SpectroscopyJ.W. Cooley, A. Abdine, M. Brown, J. Chavez, B. Lada, R.D. JiJi and I. Ubarretxena-Belandia9. An Inducible Reconstitution System for the Real-Time Kinetic Analysis of Protease Activity and Inhibition Inside the MembraneR.P. Baker and S. Urban10. Production of Recombinant Rhomboid ProteasesE. Arutyunova, R. Panigrahi, K. Strisovsky and M.J. Lemieux11. Mechanism and Inhibition of Rhomboid ProteasesK. Strisovsky12. Enzymatic Assays for Studying Intramembrane ProteolysisD.M. Bolduc, D.J. Selkoe and M.S. Wolfe13. Methods for S¬tructural and Functional Analyses of Intramembrane Prenyltransferases in the UbiA Super FamilyY. Yang, N. Ke, S. Liu and W. Li14. Functional Study of the Vitamin K Cycle Enzymes in Live CellsJ.-K. Tie and D.W. Stafford15. Activity Assays for Rhomboid ProteasesE. Arutyunova, K. Strisovsky and J. Lemieux