David L. Tierney, Associate Professor; born 1963
B.S. Saginaw Valley State University (1989)
Ph.D. University of Michigan (1996)
NIH Postdoctoral Fellow,
Northwestern University (1996-2000)
Office: B80 Clark Hall (505) 277-2505
Lab: 280 Clark Hall (505) 277-1649
e-mail: dtierney@unm.edu Fax: (505) 277-2609
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.
Publications:
36. 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 "Modeling mononuclear BcII species by site-directed mutagenesis" Biochemistry, 2008, submitted.
35. 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, submitted.
34. H. Maeda, D. L. Tierney, P. S. Mariano, M. Bannerjee, D. W. Cho and U. C. Yoon “Crown Ether Based Heavy Metal Ion Fluorescence Sensors” Tetrahedron, 2008, in press.
33. 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.
32. 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.
31. 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.
30. 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.
29. E. A. Riley, A. K. Petros, K. A. Smith, B. R. Gibney and D. L. Tierney “Frequency-Switching Inversion-Recovery for Severely Hyperfine Shifted NMR: Evidence of Asymmetric Electron Relaxation in High-Spin Co(II)” Inorg. Chem., 2006, 45, 10016-10018.
28. R. M. Franzini, R. M. Watson, G. K. Patra, R. M. Breece, D. L. Tierney, M. P. Hendrich and C. Achim “Metal Binding to Bipyridine-Modified PNA Duplexes” Inorg. Chem., 2006, 45, 9798-9811.
27. A. L. Costello, N. P. Sharma, K.-W. Yang, M. W. Crowder and D. L. Tierney “X-Ray Absorption Spectroscopy of the Zinc Binding Sites in the Class B2 Metallo-b-Lactamase ImiS from Aeromonas veronii bv. sobria” Biochemistry, 2006, 45, 13650-13658.
26. J. Momb, P. W. Thomas, R. M. Breece, D. L. Tierney and W. Fast “The Quorum-Quenching Metallo-g- Lactonase from Bacillus thuringiensis Exhibits a Leaving Group Thio Effect” Biochemistry, 2006, 45, 13385-13393.
25. F. E. Jacobsen, R. M. Breece, W. K. Myers, D. L. Tierney, and S. M. Cohen “Model Complexes of Cobalt-Substituted Matrix Metalloproteinases: Tools for Inhibitor Design” Inorg. Chem., 2006, 45, 7306-7315.
24. E. M. Stone, A. L. Costello, D. L. Tierney, and W. Fast “Substrate-Assisted Cysteine Deprotonation in the Mechanism of Dimethylargininase (DDAH) from Pseudomonas aeruginosa” Biochemistry, 2006, 45, 5618-5630.
23. A. L. Costello, G. Periyannan, K.-W. Yang, M. W. Crowder and D. L. Tierney “Site Selective Binding of Zn(II) to Metallo-b-Lactamase L1 from Stenotrophomonas maltophilia” J. Biol. Inorg. Chem., 2006, 11, 351-358.
22. G. Periyannan, A. L. Costello, D. L. Tierney, K.-W. Yang, B. Bennett and M. W. Crowder “Sequential Binding of Cobalt(II) to Metallo-b-Lactamase CcrA” Biochemistry, 2006, 45, 1313-1320.
21. A. V. Ellis, C. F. M. Clewett, D. L. Tierney, J. L. Dewald, S. A. Curran and T. Pietraß “Electron Spin Resonance and Raman Scattering Spectroscopy of Multi-Walled Carbon Nanotubes: A Function of Acid Treatment” J. Nanosci. Nanotech., 2006, 6, 135-140.
20. P. W. Thomas, E. M. Stone, A. L. Costello, D. L. Tierney and W. Fast “The Quorum-Quenching Lactonase from Bacillus thuringiensis Is a Metalloprotein” Biochemistry, 2005, 44, 7559-7569.
19. R. M. Breece, A. L. Costello, B. Bennett, T. K. Sidgel, M. L. Mathews, D. L. Tierney and M. W. Crowder “A Five-Coordinate Metal Site in VanX” J. Biol. Chem., 2005, 280, 11074-11081.
18. D. L. Tierney, A. M. Rocklin, J. D. Lipscomb, L. Que, Jr. and B. M. Hoffman “ENDOR Studies of the Ligation and Structure of the Non-Heme Iron Site in ACC Oxidase” J. Am. Chem. Soc., 2005, 127, 7005-7013.
17. A. K. Petros, S. E. Shaner, A. L. Costello, D. L. Tierney and B. R. Gibney “Comparison of Cysteine and Penicillamine Ligands in a Co(II) Maquette” Inorg. Chem., 2004, 43, 4793-4795.
16. K. Shen, D. L. Tierney and T. Pietraß “Electron Spin Resonance of Carbon Nanotubes Under Hydrogen Adsorption” Phys. Rev. B, 2003, 68, 165418.
15. M. Carepo, D. L. Tierney, C. D. Brondino, T. C. Yang, A. Pamplona, J. Telser, I. Moura, J. J. G. Moura and B. M. Hoffman “17O ENDOR Detection of a Solvent-Derived Ni-(OHx)-Fe Bridge That is Lost Upon Activation of the Hydrogenase from Desulfovibrio gigas” J. Am. Chem. Soc., 2002, 124, 281-286.
14. D. L. Tierney, P. J. Moehs, and D. L. Hasha “1,3-Dichloro- and 1,3-Dibromotetra-n-butyldistannoxane Mixtures: Ligand Redistribution and Fluxional Dynamics in Distannoxanes” J. Organomet. Chem., 2001, 620, 211-226.
13. D. L. Tierney, H. Huang, P. Martasek, L. Roman, B. S. S. Masters, B. M. Hoffman and R. B. Silverman “ENDOR Spectroscopic Evidence for the Geometry of Binding of retro-inverso-Nw-Nitroarginine-Containing Dipeptide Amides to Neuronal Nitric Oxide Synthase” J. Am. Chem. Soc., 2000, 122, 7869-7875.
12. D. L. Tierney, H. Huang, P. Martasek, L. Roman, B. S. S. Masters, R. B. Silverman and B. M. Hoffman “ENDOR Studies of L-Arginine and NG-Hydroxy-L-Arginine Bound to all Three Holo-Nitric Oxide Synthase Isozymes” J. Am. Chem. Soc., 2000, 122, 5405-5406.
11. D. L. Tierney, G. T. Gassner, C. Luchinat, I. Bertini, D. P. Ballou and J. E. Penner-Hahn “NMR Characterization of Substrate Binding in the Phthalate Dioxygenase System” Biochemistry, 1999, 38, 11051-11061.
10. A. M. Rocklin, D. L. Tierney, V. Kofman, N. M. W. Brunhuber, B. M. Hoffman, R. E. Christoffersen, N. O. Reich, J. D. Lipscomb and L. Que, Jr. “Role of the Nonheme Fe(II) Center in the Biosynthesis of the Plant Hormone Ethylene” Proc. Natl. Acad. Sci., 1999, 96, 7905-7909.
9. D. L. Tierney, H. Huang, P. Martasek, B. S. S. Masters, R. B. Silverman and B. M. Hoffman “ENDOR Spectroscopic Evidence for the Position and Structure of NG-Hydroxy-L-Arginine Bound to Holo-Neuronal Nitric Oxide Synthase” Biochemistry, 1999, 38, 3704-3710.
8. K. Clark-Baldwin, D. L. Tierney, K. Govindaswamy, E. Gruff, C. W. Kim, J. M. Berg, S. A. Koch and J. E. Penner-Hahn “The Limitations of X-Ray Absorption Spectroscopy for Determining the Structure of Zinc Sites in Proteins: When is a Tetrathiolate not a Tetrathiolate?” J. Am. Chem. Soc., 1998, 120, 8401-8409.
7. D. L. Tierney, P. Martasek, P. E. Doan, B. S. S. Masters and B. M. Hoffman “Location of Guanidino Nitrogen of L-Arginine Substrate Bound to Neuronal Nitric Oxide Synthase (nNOS): Determination by Q-band Pulsed ENDOR Spectroscopy” J. Am. Chem. Soc., 1998, 120, 2983-2984.
6. G. R. Dieckmann, D. L. Tierney, L. M. Utshcig, D. K. McRorie, T. V. O'Halloran, J. E. Penner-Hahn, W. F. DeGrado and V. L. Pecoraro “The de novo Design of Mercury Binding Two- and Three-Helical Bundles” J. Am. Chem. Soc., 1997, 119, 6195-6196.
5. G. A. Garcia, D. L. Tierney, S. Chong, K. Clark and J. E. Penner-Hahn “X-Ray Absorption Spectroscopy of the Zinc Site in tRNA-Guanine Transglycosylase from Eschericia coli” Biochemistry, 1996, 35, 3133-3139.
4. R. T. Witkowski, K. Clark, D. L. Tierney, J. E. Penner-Hahn, L. Newman, S. Hattman and G. McLendon “The Zinc Coordination Site of the Bacteriophage Mu Translation Activating Protein Com” J. Mol. Biol., 1995, 247, 753-764.
3. D. L. Tierney, J. A. Fee, M. L. Ludwig and J. E. Penner-Hahn “X-Ray Absorption Spectroscopy of the Iron Site in E. coli Fe(III) Superoxide Dismutase” Biochemistry, 1995, 34, 1661-1668.
2. J. A. Landro, E. Schmidt, P. Schimmel, D. L. Tierney and J. E. Penner-Hahn “Thiol Ligation of Two Zinc Atoms to a Class I tRNA Synthetase: Evidence for Unshared Thiols and Role in Amino Acid Binding and Utilization” Biochemistry, 1994, 33, 14213-14220.
1. M. S. Lah , B. R. Gibney, D. L. Tierney, J. E. Penner-Hahn and V. L. Pecoraro “The Fused Metallacrown Anion Na2([Na0.5[Ga(salicylhydroximate)]4]2(m2-OH)4)- is an Inorganic Analog of a Cryptate” J. Am. Chem. Soc., 1993, 115, 5857-5858.
To Spanky...
July, 1992... to July, 2006.
A day at the home office will never be the same.
