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Research Activities

Overview

    
     

Lipid Second Messengers and Phospholipases

Characterization of Phospholipase A2

Inhibitors and Cellular Studies
 

Membrane Phenomenon and Surface Dilution Kinetics
 One of the major difficulties in studying enzymes acting in and on membranes and receptors localized therein is that biological phenomenon occur in two dimensional space rather than in the three dimensional solutions that have been traditionally studied by biochemists. In the early 1970’s, we developed a novel approach to such studies called “surface dilution” kinetics [Review: 26] which provides an overall framework for examining the action of a variety of signal transduction enzymes on surfaces. In this system the substrate concentration is expressed in surface dilution units of mole fraction and allows analysis of kinetics. We have also studied these enzymes structurally by x-ray (27) and NMR (28) where we have also examined the interaction with interfaces such as micelles. We are now applying the surface dilution phenomenon to the analysis of activators (29) and inhibitors which in general partition with the surface and must be considered in surface dilution units. This analysis is central to analyzing the activation and inhibition of signal transduction enzymes with multiple binding sites.
 

Other Novel Enzymes

Oxidized Lipids
 
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Significant References

  1. Carman, G.M., Deems, R.A., and Dennis, E.A., Lipid-Dependent Enzymes and Surface Dilution Kinetics, J.Biol.Chem., 270, 18711-18714 (1995).
  2. Segelke, B.W., Nguyen, D., Chee, R., Xuong, N.H., and Dennis, E.A., Structures of Two Novel Crystal Forms of Naja naja naja Phospholipase A2 Lacking Ca2+ Reveal Trimeric Packing, J.Mol.Biol., 279, 223-232 (1998).
  3. Plesniak, L., Yu, L., and Dennis, E.A., Conformation of Micellar Phospholipid Bound to the Active Site of Phospholipase A2, Biochemistry, 34, 4943-4951 (1995).
  4. Lefkowitz,L.J., Deems,R.A., and Dennis,E.A., Expression of Group IA Phospholipase A2 in Pichia pastoris: Identification of a Phosphatidylcholine Activator Site Using Site-Directed Mutagenesis, Biochemistry, 38 (43), 14174-14184 (1999).
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