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 tools are biophysical ones, including in particular X-ray crystallography; we also devote much energy to protein expression and protein biochemistry 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. In particular, we are interested in elucidating the molecular basis of different kinds of vancomycin resistance. 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.

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 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.

"Crystal Clear"
Exel Magazine (2016)

"New Protein Structure Holds Answers to PKU"
Pulse (Summer 2016)

View all of Pat Loll's publications

“Structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states”
Maciunas LJ, Porter N, Lee PJ, Gupta K, and Loll PJ
Acta Cryst D77: 1027-1039 (2021)

“A useful epitope tag derived from maltose binding protein”
Lénon M, Ke N, Ren G, Meuser ME, Loll PJ, Riggs P, and Berkmen M
Protein Sci. 30(6):1235-1246. doi: 10.1002/pro.4088. (2021)

“Structural insights into the activity and regulation of human Josephin-2”
Grasty KC, Weeks SD, and Loll PJ
J Struct Biol X 3:100011. doi: 10.1016/j.yjsbx.2019.100011. (2019)

"X-ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation"
Jackson MR, Loll PJ and Jorns MS
Structure 27(5):794-805.e4. doi: 10.1016/j.str.2019.03.002 (2019)

"Vancomycin Does Not Affect the Enzymatic Activities of Purified VanSA"
Upton EC, Maciunas LJ, and Loll PJ
PLoS One, 14:e0210627. DOI: 10.1371/journal.pone.0210627 (2019)

"Structural Analysis of Anesthetics in Complex With Soluble Proteins"
Loll PJ
Methods Enzymol., 603: 3-20. DOI: 10.1016/bs.mie.2018.01.016 (2018)

"A high resolution crystal structure reveals the molecular details of target recognition by bacitracin"
Economou NJ, Cocklin S, Loll PJ
Proc. Nat. Acad. Sci. USA, 110:14207-14212 (2013)

"The high resolution structure of tyrocidine A reveals an amphipathic dimer"
Loll PJ, Upton EC, Nahoum V, Economou NJ and Cocklin S
Biochim. Biophys. Acta 1838:1199-1207 (2014)

"Membrane proteins, detergents, and crystals: What is the state of the art?"
Loll PJ 
Acta Crystallogr. F70:1576-83 (2014)

"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 and 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 and 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
J Mol Biol. 385: 200-11 (2009)

"Crystal Structure of Ristocetin A in Complex with a Bacterial Cell Wall Mimetic"
Nahoum V, Spector S and 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 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)

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