Image of Loll, Patrick

Patrick Loll, Ph.D.

Professor

  • Department:Biochemistry & Molecular Biology
  • Education: PhD, Biophysics, John Hopkins University School of Medicine (1989)
Research Overview

Research Interests: X-ray crystallography, antibiotic mechanism, anesthetic mechanism, protein  aggregation disease,  polyglutamine disease, deubiquitinatin enzymes

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.
Publications

"Beyond the detergent effect: A binding site for sodium dodecyl sulfate (SDS) in mammalian apoferritin."
Liu R, Bu W, Xi J, Mortazavi SR, Cheung-Lau J, Dmochowski IJ, & Loll PJ
Acta Crystallogr. D68, 497-504 (2012)

"Recognition of Anesthetic Barbiturates by a Protein Binding Site: A High Resolution Structural Analysis."
Oakley S, Vedula SL, Bu W, Meng QC, Xi J, Liu R, Eckenhoff RG, & Loll PJ
PLoS One 7: e32070 (2012)

"A carrier protein strategy yields the structure of dalbavancin."
Economou NJ, Nahoum V, Weeks SD, Grasty KC, Zentner IJ, Townsend TM, Bhuiya MW, Cocklin S, Loll PJ
J. Am. Chem. Soc. 134: 4637-4645 (2012)

"Crystal structure of a Josephin-ubiquitin complex: Evolutionary restraints on ataxin-3 deubiquitinating activity."
Weeks SD, Grasty KC, Hernandez-Cuebas L, & Loll PJ
J. Biol. Chem. 286, 4555-4565 (2011)

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

"Crystal Structure of Ristocetin A in Complex with a Bacterial Cell Wall Mimetic."
Nahoum V, Spector S, & Loll PJ
Acta Crystallogr. D65, 832-838 (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, & 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, & 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, & Loll PJ
Proteins 77: 753-759 (2009)

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

Academic Location

Department of Biochemistry & Molecular Biology
245 North 15th Street
Mail Stop 497
Philadelphia, PA 19102
Phone: 215-762-7706
Fax: 215-762-4452

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