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Protein folding. subunit assembly. ligand interactions. hydration. dioxins and related compoundsProtein biophysics- We study protein folding and the intermolecular interactions between protein subunits of multimolecular complexes. between proteins and small ligands. and between cations and DNA. Particular emphasis is placed on the role(s) of water of hydration. Among the properties of hydrating solvent which differ from those of bulk water is the density. Changes in density manifest as changes in volume. which we measure. along with a variety of spectroscopic and other properties. Both equilibrium and kinetic data are obtained. often from the same experiments. In the refolding of ribonuclease-A. for example. two slow processes are seen which occur concurrently with different time constants and different kinetic responses to altered solution conditions. One entails a rise in volume. while the other yields a fall. Their molecular bases have been tentatively identified. In a collaborative project we have fused a leader sequence to a globular protein which is not normal secreted from the cell. The fusion product folds to the native conformation. but its folding is retarded by the presence of the leader. with implications for the control both of secretion and for folding in vivo. Lastly. in theoretical work we have developed methods for the analysis of protein secondary and tertiary structures which will aid in protein design and have implications for folding. This last project is computational and makes heavy use of graphics. Toxicology and environmental science of dioxins and related compounds- In a collaborative project we have developed methods to evaluate past exposure of people to dioxins and related compounds. Studies of Vietnam veterans exposed to Agent Orange during the war have been completed. We have also studied environmental exposure of marine animals which feed on contaminated sediments. the materials through the food chain. Laboratory studies have focused on purification and identification of proteins which bind dioxin. For this purpose we have developed an affinity purification column to which dioxin is covalently attached. An understanding of which proteins may be involved in dioxin binding will help us understand the broad and somewhat nonspecific manifestations of the toxicity caused by these compounds. Selected PublicationsRauceo JM, De Armond R, Otoo H, Kahn PC, Klotz SA, Gaur NK, Lipke PN. (2006) Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p. Eukaryot Cell. 5(10):1664-73. El Kadi N, Taulier N, Le Huerou JY, Gindre M, Urbach W, Nwigwe I, Kahn PC, Waks M. (2006) Unfolding and refolding of bovine serum albumin at acid pH: ultrasound and structural studies. Biophys J. 91(9):3397-404. Falomir-Lockhart LJ. Laborde L. Kahn PC. Storch J. Corsico B. (2006) Protein-membrane interaction and fatty acid transfer from intestinal fatty acid-binding protein to membranes. Support for a multistep process. J Biol Chem. 281(20):13979-89. Liou HL. Kahn PC. Storch J.(2002) Role of the helical domain in fatty acid transfer from adipocyte and heart fatty acid-binding proteins to membranes: analysis of chimeric proteins. Journal of Biological Chemistry. 277(3):1806-15. Zhao H. Chen MH. Shen ZM. Kahn PC. Lipke PN. (2001) Environmentally induced reversible conformational switching in the yeast cell adhesion protein alpha-agglutinin. Protein Science. 10(6):1113-23. Zhao H. Shen ZM. Kahn PC. Lipke PN. (2001) Interaction of alpha-agglutinin and a-agglutinin. Saccharomyces cerevisiae sexual cell adhesion molecules. Journal of Bacteriology. 183(9):2874-80. Grigorescu A. Chen MH. Zhao H. Kahn PC. Lipke PN. (2000) A CD2-based model of yeast alpha-agglutinin elucidates solution properties and binding characteristics. IUBMB Life. 50(2):105-13. Kajander T. Kahn PC. Passila SH. Cohen DC. Lehtio L. Adolfsen W. Warwicker J. Schell U. Goldman A.(2000) Buried charged surface in proteins. Structure. 8(11):1203-14. Kornblatt JA. Kornblatt MJ. Rajotte I. Hoa GH. Kahn PC. (1998) Thermodynamic volume cycles for electron transfer in the cytochrome c oxidase and for the binding of cytochrome c to cytochrome c oxidase. Biophysical Journal. 75(1):435-44. Helin. S.. Kahn. P.C.. Lakshmi Guha. L.. Mallows. D.J.. Steitz. T.A.. and Goldman. A. (1995). The refined x-ray structure of muconate lactonizing enzyme from Pseudomonas putida at 1.85 A resolution. J. Mol. Biol.. 254: 918-941. Lipke. P.N.. Chen. M.-H.. De Nobel. H.. Kurjan. J.. and Kahn. P.C. (1995). Homology modeling of an immunoglobulin-like variable domain in the Saccharomyces cerevisiae adhesion protein a-agglutinin. Protein Science 4: 2168-2178. Foygel. K.. Spector. S.. Chatterjee. S.. and Kahn. P. C. (1995). The volume changes of the molten globule transitions of horse heart ferricytochrome c: A thermodynamic cycle. Protein Science 4: 1426-1429. Chatterjee. S.. Suciu. D.. Dalbey. R. E.. Kahn. P. C.. and Inouye. M. (1995). Determination of Km and kcat for signal peptidase I using a full length secretory precursor. pro-OmpA-nuclease. J. Mol. Biol. 245: 311-314. |
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