Structural Genomics
A large fraction of
the predicted genes identified in genome sequencing projects code for
uncharacterized or "hypothetical" proteins. Understanding the
function of these proteins is essential if the goals of systems biology are to
be realized. At PNNL, in association with the Northeast Structural Genomics
Consortium, NMR spectroscopy is being used to determine the 3D structures of
functionally uncharacterized proteins whose sequences are not similar to the sequence
of any protein whose structure is known. With the structure of an
uncharacterized protein, one can begin to understand its function according to
structure-function principles. Structure analysis and comparison to other
structures allow development of testable functional hypotheses, particularly
when combined with proteomics information such as expression profiles and
identification of interacting proteins.
Structural Genomics Publications
NMR Structure of the Eschericia Coli Protein YacG; a Novel
Sequence Motif in the Zinc-Finger Family of Proteins. T.A. Ramelot, J.R. Cort, A.A. Yee, A. Semesi, A.M. Edwards,
C.H. Arrowsmith, and M.A. Kennedy. Proteins, 49, 289-293 (2002)
Myxoma Virus Immunomodulatory Protein M156R is a Structural Mimic
of Eukaryotic Translation Initiation Factor eIF2a. T.A. Ramelot, J.R.
Cort, A.A. Yee, F. Liu, M.B. Goshe, A.M. Edwards, R.D. Smith, C.H. Arrowsmith,
T.E. Dever, and M.A. Kennedy. J. Mol. Biol. 322, 943-954 (2002)
NMR Structure of Conserved Eukaryotic Protein ZK652.3 from C.
Elegans: a
Ubiquitin-like Fold. J.R. Cort, Y.
Chiang, D. Zheng, G.T. Montelione, and M.A. Kennedy. Proteins: Struc., Func.,
and Gen., 48, 733-736 (2002).
An NMR Approach to Structural Proteomics. A. Yee, X. Chang, A.
Pineda-Lucena, B. Wu, A. Semesi, B. Le, T. Ramelot, G.M. Lee, S. Bhattacharyya,
P. Gutierrez, A. Denisov, C.-H. Lee, J.R. Cort, G. Kozlov, J. Liao, G. Finak,
L. Chen, D. Wishart, W. Lee, L.P. McIntosh, K. Gehring, M.A. Kennedy, A.M.
Edwards, and C.H. Arrowsmith. Proc. Nat. Acad. Sci. USA 99, 1825-1830 (2002).
NMR Structure of the Hypothetical Protein Encoded by the YjbJ gene
from Escherichia coli. A. Pineda-Lucena, J. Liao, B. Wu, A. Yee, J.R. Cort, M.A.
Kennedy, A.M. Edwards, and C.H. Arrowsmith. Proteins: Structure, Function, and
Genetics, 47, 572-574 (2002).
Solution Structure of Pyrobaculum aerophilum DsrC, an Archaeal Homologue
of the gamma Subunit of Dissimilatory Sulfite Reductase. J.R. Cort, S.V. S.
Mariappan, C. Kim, M.S. Park, T.S. Peat, G.S. Waldo, T.C. Terwilliger and M.A.
Kennedy. Eur. J. Biochem. 268, 5842-5850 (2001).
NMR Structure Determination and Structure-Based Functional
Characterization of Conserved Hypothetical Protein MTH1175 from Methanobacterium
thermoautotrophicum. J.R. Cort, A. Yee, A.M. Edwards, C.H. Arrowsmith and M.A.
Kennedy. J. Struct. Funct. Genomics 1, 15-25 (2000).
Structural Proteomics of an Archaeon. D. Christendat, A. Yee, A.
Dharamsi, Y. Kluger, A. Savchenko, J.R. Cort, V. Booth, C.D. Mackereth, V.
Saridakis, I. Ekiel, G. Kozlov, K.L. Maxwell, N. Wu, L.P. McIntosh, K. Gehring,
M.A. Kennedy, A.R. Davidson, E.F. Pai, M. Gerstein, A.M. Edwards, and C.H.
Arrowsmith. Nature Struct. Biol. 7, 903-909 (2000).
Structure-Based Functional Classification of Hypothetical Protein
MTH538 from Methanobacterium thermoautotrophicum. J.R. Cort, A. Yee, A.M.
Edwards, C.H. and Arrowsmith, and M.A. Kennedy. J. Mol. Biol. 382, 189-203 (2000).