Gracy R W, Talent J M, Zvaigzne A I
Department of Biochemistry and Molecular Biology, University of North Texas Health Science Center, Fort Worth 76107, USA.
J Exp Zool. 1998;282(1-2):18-27.
Our studies focus on the mechanisms of molecular wear and tear, terminal marking, protein degradation, and how these processes are altered with age. Molecular wear and tear directly links catalysis with postsynthetic terminal marking. For example, the binding of ligands and catalysis cause conformational changes that are transmitted from the catalytic center to the site of terminal marking and enhance the rates of specific covalent modifications, such as deamidation or oxidation. These oxidations or deamidations can introduce "KFERQ motifs" into proteins, which may permit them to be recognized and transported to the site(s) of complete degradation. Terminally marked proteins accumulate in aging cells and tissues and account for many of the health problems of the elderly. Two-dimensional protein fingerprinting coupled with immunostaining permits identification and characterization of these proteins. Free-radical traps or caloric restriction, which may prevent the formation or enhance the degradation of terminally marked proteins, may be useful in the prevention or treatment of age-associated health problems, including dementia.
我们的研究集中在分子磨损、末端标记、蛋白质降解的机制，以及这些过程如何随年龄而改变。分子磨损将催化作用与合成后末端标记直接联系起来。例如，配体的结合和催化作用会引起构象变化，这种变化从催化中心传递到末端标记位点，并提高特定共价修饰（如脱酰胺或氧化）的速率。这些氧化或脱酰胺作用可将“KFERQ基序”引入蛋白质中，这可能使它们能够被识别并转运到完全降解的位点。末端标记的蛋白质在衰老细胞和组织中积累，并导致老年人的许多健康问题。二维蛋白质指纹图谱结合免疫染色可对这些蛋白质进行鉴定和表征。自由基捕获剂或热量限制，可能会阻止末端标记蛋白质的形成或增强其降解，这可能对预防或治疗与年龄相关的健康问题（包括痴呆症）有用。
