Arkansas Chemistry/Biochemistry Roger E. Koeppe II (...Recent publications.........) (......Students......................) (.........Collaborators............) (............Research interests..)

acylgramicidin

Membrane Biochemistry, Peptide Engineering, Lipid/Protein Interactions email: rk2@uark.edu

Our laboratory has primary interests in the regulation of membrane protein function, including the folding and assembly of subunits, hydrophobic matching, and mechanical coupling between proteins and lipids. Systems of study include voltage-dependent ion channels, designed membrane-spanning helical peptides, and mixed lipid systems.

Former Mentors: Robert M. Stroud, Lubert Stryer.

Former Graduate Students: William Lance Whaley, PhD 1986; Bobbie Kuntz, MS 1989; Beverly Davis Meinzer, MS 1989; Ellen Friday, PhD 1990; Martin Jeffrey Taylor, PhD 1992; Jeffrey C Fairman, PhD 1992; Denise V Greathouse, PhD 1993; Kim Chan, PhD 1993; Gwendolyn L Mattice, PhD 1994; Shalendar Mittal, MS 1997; Anthony R Jude, PhD 1998; Robyn Goforth, PhD 2001; Patrick van der Wel, PhD 2002; Sigrid Schmutzer, PhD 2002; Haiyan Sun, PhD 2003; Anna Daily, PhD 2007; Hong Gu, PhD 2008.

Current interests Folding and assembly of proteins within membranes. Anchor functions of tryptophan (Trp, or W) at the membrane/water interface. Promotion of ion transport by Trp and fluoro-Trp indoles, and other dipoles. Role of the peptide backbone for ion transport. Chemical substitutions within the peptide backbone. Use of non-genetic amino acids to study protein mechanisms. Chemical mechanisms for voltage-dependent channel gating. Development of molecular force transducers to measure the energetics of membrane thinning. Peptide based drug design.

27-residue WALP peptide 27-amino acid WALP peptide

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Selected recent publications ---- Roger E. Koeppe II

1. Vostrikov, Vitaly V., Grant, Christopher V., Daily, Anna E., Opella, Stanley J., and Roger E. Koeppe, II (2008) J. Am. Chem Soc., 130, 12584-85.
   Comparison of “Polarization Inversion with Spin Exchange at Magic Angle” and “Geometric Analysis of Labeled Alanines” Methods for Transmembrane Helix Alignment. (See this article)
2. Sun, Haiyan, Greathouse, Denise V., Andersen, Olaf S., and Roger E. Koeppe, II (2008) J. Biol. Chem., 283, 22233-43.
   On the preference of tryptophan for membrane interfaces: Insights from N-methylation of tryptophans in gramicidin channels. (See this article)
3. Daily, A.E., Greathouse, D.V., van der Wel, P.C.A and R.E. Koeppe II (2008) Biophys. J. 94, 480-491.
   Helical distortion in tryptophan and lysine anchored membrane-spanning alpha helices as a function of hydrophobic mismatch:
   A solid-state deuterium NMR investigation using the Geometrical Analysis of Labeled Alalnines method. (See this article)
4. Holt, Andrea, de Almeida, R., Nyholm, T., Loura, L., Daily, Anna, Staffhorst, R., Rijkers, D., Koeppe, R.E., II, Prieto, M., and J. A. Killian (2008) Biochemistry 47, 2638-2649.
   Is there a preferential interaction between Cholesterol and Tryptophan residues in membrane proteins? (See this article)
5. Andersen, O.S., and R.E. Koeppe II (2007) Annual Review Biophys. Biomolec. Struct. 36, 107-130.
   Bilayer Thickness and Membrane Protein Function: An Energetic Perspective. (See this article)
6. van der Wel, P.C.A., N.D. Reed, D.V. Greathouse, and R.E. Koeppe II (2007) Biochemistry 46, 7514-7524.
   Orientation and Motion of Tryptophan Interfacial Anchors in Membrane-Spanning Peptides. (See this article)
7. Bruno, M.J., R.E. Koeppe II, and O.S. Andersen (2007) Proc. Natl. Acad. Sci., USA 104, 9638-9643.
   Docosahexaenoic acid alters bilayer elastic properties. (See this article)
8. Ashrafuzzaman, Md., Lampson, M.A., Greathouse, D.V., Koeppe, R.E., II, and Andersen, O.S. (2006) J. Phys. Condens. Matter 18, S1235–S1255.
   Manipulating lipid bilayer material properties using biologically active amphipathic molecules. (See this article)
9. Siegel, D.P., V. Cherezov, D.V. Greathouse, R.E. Koeppe, II, J.A. Killian, and M. Caffrey (2006) Biophys. J. 90, 200-211.
   Transmembrane Peptides Stabilize Inverted Cubic Phases in a Biphasic Length-Dependent Manner: Implications for Protein-Induced Membrane Fusion. (See this article)
10. Pulay, P., E.M. Scherer, P.C.A. van der Wel, and R.E. Koeppe II (2005) J. Am. Chem. Soc. 127, 17488-17493.
    Importance of Tensor Asymmetry for the Analysis of 2H NMR Spectra from Deuterated Aromatic Rings. (See this article)
11. Andersen, O. S., R. E. Koeppe II, and B. Roux (2005) IEEE Trans. Nanobioscience 4, 10-20.
    Gramicidin Channels. (See this article)
12. Suchyna, T. M., S. E. Tape, R. E. Koeppe II, O. S. Andersen, F. Sachs, and P. A. Gottlieb (2004) Nature 430, 235-240.
    Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers. (See this article)
13. Koeppe, R.E., II, H. Sun, P.C.A. van der Wel, E.M. Scherer, P. Pulay, and D.V. Greathouse (2003) J. Am. Chem. Soc. 125, 12268-12276.
    Combined Experimental/Theoretical Refinement of Indole Ring Geometry Using Deuterium Magnetic Resonance and ab Initio Calculations. (See this article)
14. Goforth, R.L., A.K. Chi, D.V. Greathouse, L.L. Providence, R.E. Koeppe, II, and O.S. Andersen (2003) J. Gen. Physiol. 121, 477-493.
    Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function. (See this article)
15. Hwang, T.-C., R. E. Koeppe, II, and O. S. Andersen (2003) Biochemistry 42, 13646-13658.
    Genistein can modulate channel function by a phosphorylation-independent mechanism: Importance of hydrophobic mismatch and bilayer mechanics. (See this article)
16. Van der Wel, P.C.A., Strandberg, E., Killian, J.A., and Koeppe, R.E., II (2002) Biophys. J. 83, 1479-1488.
    Intrinsic Tilt of a Tryptophan Anchored Transmembrane a-Helix determined using 2H NMR Spectroscopy. (See this article)
17. Jude, A.R., Providence, L.L., Schmutzer, S.E., Shobana, S., Greathouse, D.V., Andersen, O.S., and Koeppe, R.E. II (2001) Biochemistry 40, 1460-1472.
    Peptide Backbone Chemistry and Membrane Channel Function: Effects of a Single Amide-to-Ester Replacement on Gramicidin Channel Structure and Function. (See this article)
18. Demmers, J.A.; van Duijn, E.; Haverkamp, J.; Greathouse, D.V.; Koeppe, R.E. II; Heck, A.J.R.; Killian, J.A. (2001) J. Biol. Chem. 276, 34501-34508.
    Interfacial positioning and stability of transmembrane peptides in lipid bilayers studied by combining hydrogen/deuterium exchange and mass spectrometry. (See this article)
19. Koeppe, R.E. II, Hatchett, J., Jude, A.R., Providence, L.L., Andersen, O.S., and Greathouse, D.V. (2000) Biochemistry 39, 2235-2242.
    Neighboring aliphatic/aromatic side chain interactions between residues 9 and 10 in gramicidin channels. (See this article)
20. Greathouse, D.V., Koeppe, R.E., II, Providence, L.L., Shobana, S., and Andersen, O.S. (1999) Methods in Enzymol. 294, 525-550.
    Design and characterization of gramicidin channels.
21. Jude, A.R., Greathouse, D.V., Koeppe, R.E., II, Providence, L.L., and Andersen, O.S. (1999) Biochemistry 38, 1030-1039.
    Modulation of gramicidin channel structure and function by the aliphatic "spacer" residues 10, 12, and 14 between the tryptophans. (See this article)
22. De Planque, M.R.R., Kruijtzer, J.A.W., Liskamp, R.M.J., Marsh, D., Greathouse, D.V., Koeppe, R.E. II, De Kruijff, B., and Killian, J.A. (1999) J. Biol. Chem. 274, 20839-46.
    Different membrane anchoring positions of tryptophan and lysine in synthetic transmembrane alpha-helical peptides. (See this article)
23. Andersen, O.S., Greathouse, D.V., Providence, L.L., Becker, M.D., and Koeppe, R.E., II (1998) J. Am. Chem. Soc. 120, 5142-5146.
    Importance of tryptophan dipoles for protein function: 5-fluorination of tryptophans in gramicidin A channels. (See this article)

The figure below illustrates the effect of the covalent lipid in acylgramicidin on a tryptophan indole ring.



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