We are interested in high resolution mass spectrometry
studies of protein post-translational modification.
Protein post-translational modification underlies most
biological processes. Moreover, the dysregulation of protein
modification plays a causative role in a number of disease
states, especially the neurodegenerative diseases. Our laboratory
studies protein modifications that occur during neurodegeneration,
and tries to understand the role of modification in disease
progression. We are also studying the role of protein modification
in the process of memory, which can involve modifications
as subtle as conformational change. We use high resolution,
Fourier Transform Mass Spectrometry (FTMS), and are equipped
for both electrospray and MALDI ionization, including MALDI
mass spectral imaging of tissues.
Selected Publications:
"Modular Organization and Identification of a Mononuclear
Iron Binding Site Within the NifU Protein", J. N. Agar,
P. Yuvaniyama, R. F. Jack, V. L. Cash, A. D. Smith, D. R.
Dean and M. K. Johnson, J. Biol. Inorg. Chem. 5, 167 177
(2000).
"NifS-directed Assembly of a Transient [2Fe-2S] Cluster
in the NifU Protein", P. Yuvaniyama, J. N. Agar, V.
L. Cash., M. K. Johnson, and D. R. Dean, Proc. Natl. Acad.
Sci. USA 97, 599-604 (2000).
"Role of the IscU Protein in Iron-Sulfur Cluster Biosynthesis:
IscS Mediated Assembly of a [Fe2S2] Cluster in IscU",
J. N. Agar, L. Zheng, V. L. Cash, D. R. Dean, and M. K.
Johnson, J. Am. Chem. Soc. 122, 2136 2137 (2000).
"IscU as a Scaffold for Iron Sulfur Cluster Biosynthesis:
Sequential Assembly of [2Fe 2S] and [4Fe 4S] Clusters in
IscU", J. N. Agar, C. Krebs, J. Frazzon, B. H. Huynh,
D. R. Dean, and M. K. Johnson, Biochemistry (Accelerated
Publication) 39, 7856 7862 (2000).
"Characterization of the NifU and NifS Fe-S cluster formation
proteins essential for viability in Helicobacter pylori",
J. W. Olson, J. N. Agar, M. K. Johnson, and R. Maier, Biochemistry
39, 16213-16219 (2000).
"Sulfur Transfer from IscS to IscU: The First Step in Iron-Sulfur
Cluster Biosynthesis, A. D. Smith, J. N. Agar, K. A. Johnson,
J. Frazzon, I. J. Amster, D. R. Dean, and M. K. Johnson,
J. Am. Chem. Soc. 123, 11103-11104 (2001).
"IscA, an Alternate Scaffold for Fe-S cluster biosynthesis",
C. Krebs, J. N. Agar, J. Frazzon, B. H. Huynh, D. R. Dean,
and M. K. Johnson, Biochemistry, 40, 11069-14080 (2001).
"Biological Iron-Sulfur Cluster Assembly", J. N. Agar,
D. R., Dean, M. K. Johnson, in Biochemistry and Physiology
of Anaerobic Bacteria , L. G. Ljungdahl, M. W. W. Adams,
L. L. Barton, J. G. Ferry, and M.K. Johnson eds., Springer-Verlag,
46-66 (2003).
"Relevance of oxidative injury in the pathogenesis of motor
neuron diseases", J. N. Agar, H. D. Durham, Amyotroph
Lateral. Scler. Other Motor Neuron Disord. 4, 232-42 (2003).
"Mutations in COX10 Result in a Defect in Mitochondrial
Heme A Biosynthesis and Account for Multiple, Early Onset
Clinical Phenotypes Associated With Isolated COX Deficiency",
Antonicka H., Leary S. C., Guercin G, Agar J. N., Horvath
R., Kennaway N. G., Harding, C. O., Jaksch M., Shoubridge
E. A., Human Molecular Genetics, 12, 2693-2702 (2003).
"Overexpression of Metallothionein Protects Cultured Motor
Neurons Against Oxidative Stress, but not Mutant Cu/Zn-Superoxide
Dismutase Toxicity", D. M. Taylor, S. Minotti, J. N.
Agar, H. D. Durham, Neurotoxicology, 25, 779-792 (2004).
"Focal Dysfunction of the Proteasome: A Pathogenic Factor
in a Mouse Model of Amyotrophic Lateral Sclerosis",
E. M. Kabashi and J. N. Agar (coauthors), D. M. Taylor,
S. Minotti, H. D. Durham, Journal of Neurochemistry, 89,
1325-1335. (2004)
"Proteasome Activity or Expression is Not Altered by Activation
of Heat Shock Transcription Factor HSF1 in Cultured Fibroblast
and Myoblasts", D. M. Taylor, E. Kabashi, J. N. Agar,
S. Minnoti, H. D. Durham., Cell Stress and Chaperones,10:230-41
(2005).
NifS-mediated assembly of [4Fe-4S] clusters in the N-
and C-terminal domains of the NifU scaffold protein",
Smith AD, Jameson GN, Dos Santos PC, Agar JN, Naik S, Krebs
C, Frazzon J, Dean DR, Huynh BH, Johnson MK. Biochemistry.
2005 Oct 4;44(39):12955-69.
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