Office: CHCB 204
My laboratory is devoted to understanding structure/function relationships in metalloproteins. There are three current areas of biochemical research. (1) We study the prion protein, the causative agent of infectious amyloid diseases include scrapie, mad cow disease, and Creutzfeld-Jakob disease. We seek to understand the conformational changes that occur in the prion protein when it converts to the disease-causing state, which we hope will lead to therapies for this deadly disease. (2) We study how amino acid radicals modulate electron transfer through the polypeptide backbone using the blue copper protein azurin. (3) We study the structure and mechanism of tyramine beta monooxygenase, a copper enzyme involved in neurotransmitter biogenesis.
Our work is conducted in an atmosphere that emphasizes and exploits multidisciplinary approaches to research. Our funding sources have also been diverse and include support form the NIH, NSF, DOE, and DOD. Molecular biology techniques help to produce sufficient quantities of protein and allow structural variants to be made. Once protein is purified, the mechanistic and structural studies are carried out using a variety of biophysical and spectroscopic techniques. These methods include UV-Vis spectroscopy, Fluorescence, Electron Paramagnetic Resonance (EPR) spectroscopy, Isothermal Titration Calorimetry, Circular Dichroism, and Mass Spectrometry. My group uses a broad range of biochemistry techniques to learn more about protein structure and function - and we love playing with the instruments along the way!
University of Massachusetts, B.S. Chemistry
Montana State University, Bozeman Ph.D. Biochemistry
California Institute of Technology NIH Postdoctoral Scholar
Affiliate Faculty, Department of Chemistry and Biochemistry
Center for Biomolecular Structure and Dynamics
Graduate Program in Biomolecular Structure and Dynamics
Selected Recent Publications
Mechanism of the Insect Enzyme, Tyramine beta-Monooxygenase, Reveals Differences from the Mammalian Enzyme, Dopamine beta-Monooxygenase. CR Hess, MA McGuirl, and JP Klinman, J. Biol. Chem. 283(6):3042-9 (2008).
Probing Structural Differences in Prion Protein Isoforms by Tyrosine Nitration. CW Lennon, HD Cox, SP Hennelly, SJ Chelmo, and MA McGuirl, Biochemistry 46: 4850-60 (2007).
Modulation of the Electrochemical Behavior of Tyrosyl Radicals by the Electrode Surface. MC Machczynski, KP Kuhl, and MA McGuirl, Anal. Biochem. 362:89-94 (2007).
Peer Reviewed Publications
1. Hydroxylase Activity of Met471Cys Tyramine β-Monooxygenase. CR Hess, Z Wu, A Ng, EE Gray, MA McGuirl, and JP Klinman. J. Amer. Chem. Soc. 130(36) 13111-44 (2008)
2. Mechanism of the Insect Enzyme, Tyramine beta-Monooxygenase, Reveals Differences from the Mammalian Enzyme, Dopamine beta-Monooxygenase. CR Hess, MA McGuirl, and JP Klinman, J. Biol. Chem. 283(6):3042-9 (2008).
3. Modulation of the Electrochemical Behavior of Tyrosyl Radicals by the Electrode Surface. MC Machczynski, KP Kuhl, and MA McGuirl, Anal. Biochem 362:89-94 (2007).
4 Probing Structural Differences in Prion Protein Isoforms by Tyrosine Nitration. CW Lennon, HD Cox, SP Hennelly, SJ Chelmo, and MA McGuirl, Biochemistry 46: 4850-60 (2007).
5. Expression and Characterization of Recombinant Tyramine β-Monooxygenase from Drosophila: A Monomeric Copper-Containing Hydroxylase. E.E. Gray, S.N. Small, and M.A. McGuirl, Prot Exp Purif 47:162-70 (2006).
6. Structural Studies Of Apo-NosL, an Accessory Protein of the Nitrous Oxide Reductase System: Insights from Structural Homology with MerB, a Mercury Resistance Protein. L.M. Taubner,M.A. McGuirl, D.M. Dooley, V. Copié Biochemistry 45: 12240-12252 (2006)
7. 35. 1H, 13C, 15N Backbone and Sidechain Resonance Assignments for the 18 kDa Apo-NosL, a Novel Copper(I) Containing Protein from Achromobacter cycloclastes.L. Taubner, M.A. McGuirl, D.M. Dooley, and V. Copié Letter to the Editor: J. Biomolec. NMR. 29:211-2 (2004).
8. Cloning, Heterologous expression, and characterization of recombinant Class II cytochromes c from Rhodopseudomonas palustris.M. A. McGuirl , J.C. Lee, J. Lyubovitsky,C. Thanyakoop J. H. Richards, J.R. Winkler, and H.B. Gray Biochim Biophys Acta, 1619: 23-8 (2002).
9. Expression, Purification, and Characterization of NosL, a Novel Cu(I) Protein of the Nitrous Oxide Reductase (nos) Gene Cluster, Michele A. McGuirl, John A. Bollinger, and David M. Dooley, J. Biol. Inorg. Chem., 6, 189-195 (2001)
10. Structures of the Cu(I) and Cu(II) Forms of Amine Oxidases from X-ray Absorption Spectroscopy, D.M. Dooley, R.A. Scott, P.F. Knowles, C.M. Colangelo, M.A. McGuirl, and D.E. Brown, J. Amer. Chem. Soc., 120 2599-2605 (1998).
11. The nos (Nitrous Oxide Reductase) Gene Cluster from the Soil Bacterium Achromobacter Cycloclastes: Cloning, Sequence Analysis, and Expression, M.A. McGuirl, L. K. Nelson, J. A. Bollinger, Y.-K. Chan, and D. M. Dooley, J. Inorg. Biochem., 70, 155-169 (1998).
12. Cyanide as a Copper-Directed Inhibitor of Amine Oxidases: Implications for the Mechanism of Amine Oxidase, M. A. McGuirl, D. E. Brown, and D. M. Dooley, J. Biol. Inorg. Chem., 2, 336-342 (1997).
13. Crystal Structure of a Eukaryotic (Pea Seedling) Copper-Containing Amine Oxidase at 2.2 Å Resolution, V. Kumar, D. M. Dooley, H. C. Freeman, J. M. Guss, I. Harvey, M. A. McGuirl, M. C. J. Wilce, and V. M. Zubak, Structure, 4, 943-955 (1996).
14. Spectroscopic Studies of the Active Site of Galactose Oxidase, P. F. Knowles, R. D. Brown III, S. H. Koenig, S. Wang, R. A. Scott, M. A. McGuirl, D. E. Brown, and D. M. Dooley, Inorg. Chem., 34, 3895-3902 (1995).
15. Mechanistic Studies of Copper/Topa Amine Oxidases, D. M. Dooley, D. E. Brown, M. A. McGuirl, and L. J. Sears, Biochemistry of Vitamin B6 and PQQ, 253-257 (1994).
16. Purification and Characterization of Pea Seedling Amine Oxidase for Crystallization Studies, M. A. McGuirl, C. D. McCahon, K. A. McKeown, and D. M. Dooley, Plant Physiol, 106, 1205-1211 (1994).
17. Purification and Active-Site Characterization of Equine Plasma Amine Oxidase, S. R. Carter, M. A. McGuirl, D. E. Brown and D. M. Dooley, J. Inorg. Biochem., 56, 127-141 (1994).
18. Structure of the Topa-semiquinone Catalytic Intermediate of Amine Oxidase as Revealed by Magnetic Interactions with Exchangeable 2H and 1H Nuclei, K. Warncke, G. T. Babcock, D. M. Dooley, M. A. McGuirl and J. McCracken, J. Amer. Chem. Soc., 116, 4028-4037 (1994).
19. Intramolecular Electron Transfer Rate Between Active-site Copper and Topa Quinone in Pea Seedling Amine Oxidase, P. N. Turowski, M. A. McGuirl and D. M. Dooley, J. Biol. Chem., 268, 17680-17682 (1993).
20. Crystallization and Preliminary Crystallographic Characterization of the Copper-Containing Amine Oxidase from Pea Seedlings, V. Vignevich, D. M. Dooley, J. M. Guss, I. Harvey, M. A. McGuirl and H. C. Freeman, J. Mol. Biol. 229, 243-245 (1993).
21. Pulsed EPR Studies of the Semiquinone State of Copper-Containing Amine Oxidases, J. McCracken, J. Peisach, C. E. Cote, M. A. McGuirl and D. M. Dooley, J. Amer. Chem. Soc. 114, 3715-3720 (1992).
22. Evidence for Copper and 3,4,6-trihydroxyphenylalanine Quinone Cofactors in an Amine Oxidase from the Gram-negative Bacterium Escherichia Coli K-12, R. A. Cooper, P. F. Knowles, D. E. Brown, M. A. McGuirl and D. M. Dooley, Biochem. J. 288, 337-340 (1992).
23. The Organic Cofactor in Copper-Containing Amine Oxidases: Resonance Raman Spectra Are Consistent with the Presence of Topa Quinone (6-Hydroxy dopa Quinone) in the Active Site, D. E. Brown, M. A. McGuirl, D. M. Dooley, S. M. Janes, D. Mu and J. P. Klinman, J. Biol. Chem. 266, 4049-4051 (1991).
24. Spectroscopic Studies of the Copper Sites in Pseudomonas stutzeri N2O Reductase, D. M. Dooley, M. A. McGuirl, A. C. Rosenzweig, J. A. Landin, R. A. Scott, W. G. Zumft, F. Devlin and P. J. Stephens, Inorg. Chem. 30, 3006-3011 (1991).
25. A Cu(I)-Semiquinone State in Substrate-Reduced Amine Oxidases, D. M. Dooley, M. A. McGuirl, D. E. Brown, P. N. Turowski, W. S. McIntire and P. F. Knowles, Nature 349, 262-264 (1991).
26. Coordination Chemistry of Copper-Containing Amine Oxidases: Nuclear Magnetic Relaxation Dispersion (NMRD) Studies of Solvent Water Exchange, Inhibitor and Substrate Binding, and Protein Association, D. M. Dooley, M. A. McGuirl, C. E. Cote, P. F. Knowles, M. Spiller, R. D. Brown, III and S. H. Koenig, J. Amer. Chem. Soc. 113, 754-761 (1991).
27. Characterization of the Active Site of Arthrobacter P1 Methylamine Oxidase: Evidence for Copper-Quinone Interactions, D. M. Dooley, W. C. McIntire, M. A. McGuirl, C. E. Cote and J. L. Bates, J. Amer. Chem. Soc. 112, 2782-2789 (1990).
28. Methylamine Oxidase from Arthrobacter P1 as a Prototype of Eukaryotic Plasma Amine Oxidase and Diamine Oxidase, W. S. McIntire, D. M Dooley, M. A. McGuirl, C. E. Cote and J. L. Bates, J. Neural Transm. 32, 315-318 (1990).
29. Studies on the Active Site of Pig Plasma Amine Oxidase, D. Collison, P. F. Knowles, F. E. Mabbs, F. X. Rius, I. Singh, D. M. Dooley, C. E. Cote and M. A. McGuirl, Biochem. J. 264, 663-669 (1989).
30. The Generation of an Organic Free Radical in Substrate-Reduced Pig Kidney Diamine Oxidase-Cyanide, D. M. Dooley, M. A. McGuirl, J. Peisach and J. McCracken, FEBS Lett. 214, 274-278 (1987).
31. The Organic Cofactor in Plasma Amine Oxidase: Evidence For Pyrroloquinolinequinone and Against Pyridoxal Phosphate, P. F. Knowles, K. B. Pandeya, F. X. Rius, C. M. Spencer, R. S. Moog, M. A. McGuirl and D. M. Dooley, Biochem. J. 241, 603-608 (1987).
32. Evidence for Methoxatin (Pyrroloquinolinequinone) as the Cofactor in Bovine Plasma Amine Oxidase from Resonance Raman Spectroscopy, R. S. Moog, M. A. McGuirl, C. E. Cote and D. M. Dooley, Proc. Natl. Acad. Sci. (USA) 83, 8435-8439 (1986).
33. Spectroscopic Studies of Pig Kidney Diamine Oxidase-Anion Complexes, D. M. Dooley and M. A. McGuirl, Inorg. Chim. Acta 123, 231-236 (1986).
34. Thermodynamics of Azide and Thiocyanate Binding to Bovine Copper-Zinc Super-oxide Dismutase, D. M. Dooley and M. A. McGuirl, Inorg. Chem. 25, 1261-1264 (1986).
35. Azide and Fluoride Binding to E. Coli Iron Superoxide Dismutase as Studied by Solvent Nuclear Magnetic Relaxation Dispersion, D. M. Dooley, T. F. Jones, J. L. Karas, M. A. McGuirl, R. D. Brown, III and S. H. Kosnig, J. Amer. Chem. Soc. 109, 721-725 (1987).
1. Copper Proteins with Type 2 Sites. M.A. McGuirl and D.M. Dooley in Encyclopedia of Inorganic Chemistry, R.B. King, Ed. Wiley, New York (2005).
2. Copper-containing Oxidases, by Michele A. McGuirl and David M. Dooley, Current Opinion in Chemical Biology, 3:138-144 (1999).
3. Critical Commentary on: “Amidation of Bioactive Peptides: The Structure of the Peptidylglycine a-Hydroxylating Monooxygenase by S.T. Prigge, A.S. Kolhekar, B.A. Eipper, R.E. Mains and L.M. Amzel, Science 278, 1300-1305 (1997),” M.A. McGuirl and D. M. Dooley, ChemTracts-Inorganic Chemistry, 11, 911-917 (1998).