David L. Tierney


Associate Professor
Chair, Graduate Advising

B.S., Saginaw Valley State University (1989)
Ph.D., University of Michigan (1996)
NIH Postdoctoral Fellow, Northwestern University (1996-2000)

Contact Information
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Tierney Lab Web Site

Physical Inorganic and Bioinorganic Chemistry

Our research in Bioinorganic Chemistry is geared to the elucidation of structure/function relationships in metalloenzyme active sites, to gain a deeper understanding of enzyme mechanism. Our overriding interest is in the use of Co(II) as a spectroscopic probe of metal sites in proteins. The Co(II) ion is particularly well-suited to the study of Zn biochemistry. Unlike the colorless, non-magnetic 3d10 Zn(II) ion, Co(II) is 3d7 and as a consequence, is paramagnetic and it's complexes are highly colored. Favorable electronic properties make Co(II) complexes accessible by nearly all magnetic resonance techniques. The extraction of structural properties from spectroscopic observation is often hindered by the presence of substantial spin-orbit coupling and low-lying excited states. Consequently, much of the necessary baseline correlations have yet to be developed. Our lab is involved the preparation of an extensive library of Co(II) model compounds, encompassing four-, five- and six-coordinate complexes, with varying contributions from N, O and S donors. These studies allow precise correlation with structural motifs that are regularly encountered in metalloenzyme active sites. Development of these structural correlations involves characterization of both the physical and electronic structure of the metal site. We use a wide array of paramagnetic resonance techniques, electron paramagnetic resonance (EPR) at both X-band (9 GHz) and Q-band (35 GHz), electron-nuclear double resonance (ENDOR) also at both X-band and Q-band, nuclear magnetic resonance (NMR) at 100, 300 and 500 MHz and NMR relaxometry (NMRD). We maintain all of the above instrumentation in-house. The concurrent application of all of these techniques affords an unprecedented level of structural and bonding detail through interrogation of electron-nuclear hyperfine couplings from both points of view - that of the electron, and that of the nucleus. Each approach gives unique information; each has its limitations. For example, EPR and ENDOR, which give information regarding the symmetry and ligation of a metal ion, are typically performed at cryogenic temperatures on frozen solutions, offering access to trapped intermediates. In contrast, NMR and NMRD experiments, which give information regarding more distant structure, are carried out at or near room temperature on fluid solutions, offering access to dynamic information. We use all of the above to study the metal sites in Zn enzymes involved in bacterial proliferation, including metallo-b-lactamases, which confer resistance to penicillins, and the AHL lactonase, which allows bacteria to display group behavior, delaying virulence until a "quorum" population density has been attained. More recently, we have begun work on characterization of Co(II) model compounds relevant to matrix metalloproteinases (MMPs), which have been implicated in the metastasis of cancers and other tumors, through MMP-mediated breakdown of connective tissues. All of these enzymes use one or two Zn ions at their active sites, and all of them remain active when Co is substituted for Zn. We use x-ray absorption spectroscopy (XAS) to compare the structures of the native Zn and Co-substituted proteins. The suite of spectroscopic tools we employ alows us to study stable enzyme resting states, with and without bound substrates/inhibitors/products, and catalytic intermediates through rapid-freezing techniques. These studies are designed to define the key structural details that will lead to the development of effective mechanism-based inhibitors for these clinically important enzymes.


V. S. Thoi, J. L. Stork, E. T. Niles, E. C. Depperman, D. L. Tierney and S. M. Cohen “Diamidodipyrrins: Versatile Bipyrrolic Ligands with Multiple Binding Modes” Inorg. Chem., 2008, 47, 10533-10541.

L. A. Abriata, L. J. Gonzalez, L. I. Llarrull, P. E. Tomatis, W. K. Myers, A. L. Costello, D. L. Tierney and A. J. Vila “Engineered Mononuclear Variants in Bacillus cereus Metallo-b-lactamase BcII are Inactive” Biochemistry, 2008, 47, 8590-8599.

W. K. Myers, E. N. Duesler and D. L. Tierney “Integrated Paramagnetic Resonance of High-Spin Co(II) in Axial Symmetry: Chemical Separation of Dipolar and Contact Electron-Nuclear Couplings” Inorg. Chem., 2008, 47, 6701-6710.

H. Maeda, D. L. Tierney, P. S. Mariano, M. Bannerjee, D. W. Cho and U. C. Yoon “Lariat-Crown Ether Based Fluorescence Sensors for Heavy Metal Ions” Tetrahedron, 2008, 64, 5268-5278.

L. A. Yatsunyk, J. A. Easton, L. R. Kim, S. A. Sugarbaker, B. Bennett, R. M. Breece, I. I. Vorontsov, D. L. Tierney, M. W. Crowder and A. C. Rosenzweig “Structure and Metal binding Properties of ZnuA, a Periplasmic Zinc Transporter from Eschericia coli” J. Biol. Inorg. Chem., 2008, 13, 271-288.

A. R. Reddi, T. R. Guzman, R. M. Breece, D. L. Tierney and B. R. Gibney “Deducing the Energetic Cost of Protein Folding in Zinc Finger Proteins Using Designed Metallopeptides” J. Am. Chem. Soc., 2007, 129, 12815-12827.

J. M. Gonzalez, F. J. Medrano, A. L. Costello, D. L. Tierney and A. J. Vila “The Zn2 Position in Metallo-b-Lactamases is Critical for Activity: A Study of Chimeric Metal Sites on a Conserved Protein Scaffold” J. Mol. Biol., 2007, 373, 1141-1156.

J. M. Barrio, J. M. Gonzalez, M. N. Lisa, A. L. Costello, M. del Peraro, P. Carloni, B. Bennett, D. L. Tierney, A. S. Limansky, A. M. Viale and A. J. Vila “The Metallo-b-Lactamase GOB is a Mono-Zn(II) Enzyme with a Novel Active Site” J. Biol. Chem., 2007, 282, 18286-18293.