This research is part of an effort to better understand the molecular mechanisms underlying human nervous system development and function, as well as the pathogenesis of certain neurogenetic disorders. Our studies have focused on structural and active site properties of the human neuron specific proteins, lysosomal hydrolases, other proteins (particularly those peptides and proteins that interact with excitable membranes), receptors and venom toxins. Proteins are purified from both human and animal tissues using affinity chromatography, electrophoretic separation, and high performance liquid chromatography. Amino acid sequence analysis is carried out on neuronal and non-neuronal proteins and venom toxins. Peptide maps of both normal and mutant proteins are generated using chemical (cyanogen bromide) and enzymatic (trypsin, thermolysin, V8 protease) cleavage. The identification of carbohydrate attachment sites, sulfhydryl residues, and intra-chain disulfide residues is used to predict protein structure. Alkylating agents and enzyme inhibitors are used to define active sites. From the primary protein sequence, hydrophobic and hydrophilic domains of the protein are identified. Information obtained from these protein structure studies permits the design of oligonucleotides and peptides that are synthesized for collaborative research involving antibody production, cDNA cloning, DNA sequence analysis and in vitro mutagenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002344-05
Application #
3880915
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Zhou, Yuedan; Oskolkov, Nikolay; Shcherbina, Liliya et al. (2016) HMGB1 binds to the rs7903146 locus in TCF7L2 in human pancreatic islets. Mol Cell Endocrinol 430:138-45
Rossi, Leonardo; Martin, Brian M; Hortin, Glen L et al. (2006) Inflammatory protein profile during systemic high dose interleukin-2 administration. Proteomics 6:709-20
Orvisky, Eduard; Drake, Steven K; Martin, Brian M et al. (2006) Enrichment of low molecular weight fraction of serum for MS analysis of peptides associated with hepatocellular carcinoma. Proteomics 6:2895-902
Fujigaki, Hidetsugu; Saito, Kuniaki; Lin, Felix et al. (2006) Nitration and inactivation of IDO by peroxynitrite. J Immunol 176:372-9
Martin, Brian M; Karczewska, Emilia; Pliszka, Barbara (2006) Effect of nucleotide on interaction of the 567-578 segment of myosin heavy chain with actin. Biochim Biophys Acta 1764:217-22
Lu, Xuefeng; Li, Ling; Wu, Rui et al. (2006) Kinetic analysis of Pseudomonas aeruginosa arginine deiminase mutants and alternate substrates provides insight into structural determinants of function. Biochemistry 45:1162-72
Rossi, Leonardo; Moharram, Ramy; Martin, Brian M et al. (2006) Detection of human MCP-4/CCL13 isoforms by SELDI immunoaffinity capture. J Transl Med 4:5
Moharram, Ramy; Maynard, Dawn; Wang, Eric S et al. (2006) Reexamination of the cysteine residues in glucocerebrosidase. FEBS Lett 580:3391-4
Hortin, Glen L; Shen, Rong-Fong; Martin, Brian M et al. (2006) Diverse range of small peptides associated with high-density lipoprotein. Biochem Biophys Res Commun 340:909-15
Kaplan, B; Martin, B M; Cohen, H I et al. (2005) Primary local orbital amyloidosis: biochemical identification of the immunoglobulin light chain kappaIII subtype in a small formalin fixed, paraffin wax embedded tissue sample. J Clin Pathol 58:539-42

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