Abstract

This proposal involves multinuclear, multifield, and multiphase NMR investigations of the metal sites in metalloproteins. The primary metal nuclei that will be examined are 113Cd and 67Zn. The work with 113Cd continues successful use of Cd2+ as a """"""""spin spy"""""""" for the function of Zn2+ in carboxypeptidase and for probing protoporphyrin dependent proteins, such as hemoglobin. Low temperature 67Zn NMR experiments on carboxypeptidase will be performed to test the strategy of replacing Zn2+ with Cd2+. New model compounds of cadmium with a variety of coordination environments will be synthesized and studied by solution and single crystal NMR. Emphasis will be given to the preparation of ionic compounds that hold the promise of yielding crystals sufficiently large for single crystal NMR experiments that can provide 113Cd shielding tensors. Development of ab initio MO methods for calculating these tensors will continue in parallel with the experimental efforts to guide interpretation of the NMR data.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM026295-19
Application #
2684703
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1979-04-01
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
19
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352

  Publications

Lipton, Andrew S; Bergquist, Catherine; Parkin, Gerard et al. (2003) Solid-State 67Zn NMR spectroscopic studies and ab initio molecular orbital calculations on a synthetic analogue of carbonic anhydrase. J Am Chem Soc 125:3768-72
Lipton, Andrew S; Wright, Terri A; Bowman, Michael K et al. (2002) Solid-state (67)zn NMR spectroscopy in bioinorganic chemistry. Spectra of four- and six-coordinate zinc pyrazolylborate complexes obtained by management of proton relaxation rates with a paramagnetic dopant. J Am Chem Soc 124:5850-60
Lipton, Andrew S; Smith, Mark D; Adams, Richard D et al. (2002) 67Zn solid-state and single-crystal NMR spectroscopy and X-ray crystal structure of zinc formate dihydrate. J Am Chem Soc 124:410-4
Lipton, A S; Buchko, G W; Sears, J A et al. (2001) 67Zn solid-state NMR spectroscopy of the minimal dna binding domain of human nucleotide excision repair protein XPA. J Am Chem Soc 123:992-3
Lipton, A S; Sears, J A; Ellis, P D (2001) A general strategy for the NMR observation of half-integer quadrupolar nuclei in dilute environments. J Magn Reson 151:48-59
McAteer, K; Lipton, A S; Kennedy, M A et al. (1996) A multiphase 113Cd NMR investigation of metalloporphyrin reorientation in cadmium-substituted myoglobin. Solid State Nucl Magn Reson 7:229-38
Koons, J M; Ellis, P D (1995) Applicability of factor analysis in solid state NMR. Anal Chem 67:4309-15
Ellis, P D (1989) 113Cd NMR of Cd2+-substituted carboxypeptidase. Support for a hexa-coordinate metal ion in the presence of inhibitors. J Biol Chem 264:3108-10
Ellis, P D; Marchetti, P S; Strang, P et al. (1988) Cadmium-substituted skeletal troponin C metal binding investigations and sequence assignment of the cadmium-113 resonances. J Biol Chem 263:10284-8
Bhattacharyya, L; Marchetti, P S; Ellis, P D et al. (1987) Nuclear magnetic resonance investigation of cadmium 113 substituted pea and lentil lectins. J Biol Chem 262:5616-21

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