Physician Image

Patrick Loll, Ph.D.

Professor

  • Department: Biochemistry and Molecular Biology
  • Research interests: X-ray crystallography, antibiotic mechanism, anesthetic mechanism, protein  aggregation disease,  polyglutamine disease, deubiquitinatin enzymes
  • Education: Ph.D (1989) Biophysics, John Hopkins University School of Medicine
Research

Research in my lab revolves around molecular structure. The underlying goal for all our projects is to understand biologically important processes at the molecular level. Our principal tool is X-ray crystallography; we also devote much energy to protein expression, protein biochemistry, spectroscopy, and enzymology to support the structural efforts. Specific areas of interest include:

  • Large natural product antibiotics. We are applying structural, computational, and biophysical methods to deepen our understanding of how antibiotics like vancomycin, ramoplanin, tyrocidine, and bacitracin function. We hope to use this information to design novel drugs to combat antibiotic resistance.

  • The structural basis of drug action. We are interested in probing the interactions between drugs and their protein targets at the structural level. Currently, we are examining the binding of general anesthetics to model protein targets, with an eye toward elucidating the structural determinants that control anesthetic recognition.

  • Deubiquitylation by Josephin proteins. Ataxin-3 and other Josephin proteins catalyze the degradation of poly-ubiquitin chains, modulating signals controlling protein breakdown and trafficking. We are using structural and biochemical approaches to study the function of these enzymes.

  • The molecular mechanism of polyglutamine disease. We are studying ataxin-3, the causative agent of the neurodegenerative Machado-Joseph disease, using structural, ultrastructural, biochemical, and biophysical methods to understand how expansion of polyglutamine tracts leads to protein misfolding, fibril formation, and neuronal death.

  • The structural biology of membrane proteins. Many of the most fascinating and crucial processes which occur in living cells are modulated by integral membrane proteins. Our lab is studying a number of different membrane-bound enzymes, receptors, and transport proteins; in addition, a substantial effort focuses on the development of crystallization methodologies for these molecules.

Selected References

“The structural biology of molecular recognition by vancomycin" 
Loll, PJ and Axelsen, PH 
Ann. Rev. Biophys. Biomolecular Struct.  29: 265-289 (2000).

“An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel beta fibrils” 
Bevivino, AE and Loll, PJ 
PNAS USA, 98: 11955-11960 (2001).

“Structural basis for high affinity volatile anesthetic binding in a natural 4-helix bundle protein"
Liu, R, Loll, PJ, and Eckenhoff, RG
FASEB J.,19: 567-576 (2005).

“2.0 Å crystal structure of prostaglandin H2 synthase-1 reconstituted with a manganese porphyrin cofactor”
Gupta, K, Selinsky,  BS and Loll, PJ 
Acta Crystallogr. D62: 151-156 (2006).

“Ligation independent cloning vectors for expression of SUMO fusions”
Weeks, SD, Drinker, M, Loll, PJ
Prot. Expr. Purif. 53: 40-50 (2007) .

“Vancomycin forms ligand-mediated supramolecular complexes”
Loll, PJ, Derhovanessian, A, Shapovalov, MV, Kaplan, J, Yang, L, Axelsen, PH
J Mol Biol. 385: 200-11 (2009) .

“A unitary anesthetic-binding site at high resolution”
Vedula LS, Brannigan G, Economou NJ, Xi J, Hall MA, Liu R, Rossi MJ, Dailey WP, Grasty KC, Klein ML, Eckenhoff RG, and Loll PJ
J. Biol. Chem. 284: 24176-84 (2009).

“A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential Lipid II docking interface”
Hamburger, JB, Hoertz, AJ, Lee, A, Senturia, RJ, McCafferty, DG, and Loll, PJ 
Proc. Nat. Acad. Sci. USA, 106: 13759-64 (Track 2 submission) (2009).

“Crystal structures of Lys-63-linked tri- and di-ubiquitin reveal a highly extended chain architecture”
Weeks, SD, Grasty, KC, Hernandez-Cuebas, L, and Loll, PJ
Proteins 77: 753-759 (2009).

Contact

  • Drexel University College of Medicine
  • 245 N 15th St, MS 497
    Philadelphia, PA 19102
  • Phone: work 215-762-7706
  • Fax: fax 215-762-4452

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