Research Interests: Family 18 Chitinases and Related Proteins: Structure and Function in Tissue Remodeling; Glycoprotein Degradation in Human Disease. My laboratory has studied how two kinds of hydrolytic enzymes, glycosidases
and proteases, degrade glycoproteins in the lysosomes. One of the
lysosomal glycosidases called Chitobiase belongs to a special
family of proteins that hydrolyze the polysaccharide chitin
(see Figure 1 ). All Family 18 glycosidases
consist of a common barrel-like protein structure ["(ß/ In glycosidase Family 18 there also is a very intriguing subgroup of chitinase-related proteins. Through natural evolution these members have lost their catalytic potential because the reactive ß4 glutamic acid in the substrate groove has been substituted by non-active amino acids. Not much is currently known about the physiological function of these inactive family members. Based on their structure, they likely bind chitin-related polysaccharides or the sugar-chains of glycoproteins. Because there appears to be a limited time and location of their occurrence in specific tissues, the binding of an oligosaccharide would then regulate via signal transduction pathways various kinds of tissue remodeling and/or differentiation. It is likely that important genes ultimately will be turned on or off by these molecular events to provide changes in metabolism necessary for a new physiological state. We are studying one member of the inactive chitinase-related protein group called Breast Regression Protein, BRP39. It was first discovered in specific types of breast cancer cells from mice. BRP39 is also expressed by the mammary gland during involution at the termination of breastfeeding when the structure and function of the gland naturally revert to the non pregnant state. A major research goal is to determine the exact role that BRP39 plays in this remarkable physiological process. Once we have learned how BRP39 works during the normal process of mammary gland involution, we plan to use this information to help reveal any improper behavior in the breast cancer cells where it was originally discovered. Our beginning hypothesis is that BRP39 physiologically acts as a protective signaling factor that metabolically designates which cells are to survive the drastic tissue remodeling taking place during involution. We suspect cancer cells may have developed ways to use this "protectin" feature of BRP39 to enhance their viability and metastatic potential (Figure 3). Representative Publications: Aronson, NN Jr. Aspartylglycosaminuria: biochemistry and molecular biology. Biochim Biophys Acta 1999; 1455(2-3):139-154. Liu B, Ahmad W, Aronson NN Jr. Structure of the human gene for lysosomal di-N-acetylchitobiase. Glycobiology 1999; 9(6):589-593. Liu Y, Guan C, Aronson NN Jr. Site-directed mutagenesis of essential residues involved in the mechanism of bacterial glycosylasparaginase. J. Biol. Chem. 1998; 273:9688-9694. Aronson NN Jr, Blanchard CJ, Madura JD. Homology modeling of glycosyl hydrolase family 18 enzymes and proteins. J. Chem. Inf. Comput. Sci. 1997; 37:999-1005. Ahmad W, Li S, Chen H, Tuck-Muller CM, Pittler SJ, Aronson, NN Jr. Lysosomal chitobiase (CTB) and the G-protein gamma 5 subunit (GNG5) genes co-localize to human chromosome 1p22. Cytogenet. Cell. Genet. 1995; 71(1):44-46. Fisher KJ, Aronson NN, Jr. Cloning and expression of the cDNA sequence encoding the lysosomal glycosidase di-N-acetylchitobiase. J. Biol. Chem. 1992; 267(27):19607-19616. Fisher KJ , Aronson NN, Jr. Characterization of the cDNA and genomic sequence of a G protein gamma subunit (gamma 5). Mol. Cell Biol. 1992; 12(4):1585-1591. Aronson NN Jr, Backes M, Kuranda, MJ. Rat liver chitobiase; purification, properties, and the role in the lysosomal degradation of Asn-linked glycoproteins. Arch. Biochem. Biophys. 1989; 272(2):290-300. Kuranda MJ, Aronson NN Jr. A di-N-acetylchitobiase activity is involved in the lysosomal catabolism of asparagine-linked glycoproteins in rat liver. J. Biol Chem. 1986; 261:5803-5809.
 
The URL for this page is http://southmed.usouthal.edu/com/biochem/aronson.html
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fold"] with a groove on its surface designed to bind a hexasaccharide length
of chitin. A crystal structure for a Family 18 chitinase from the
bacteria S. marcescens (Chitinase A) is known and it serves
as a model for the other family members (
