Sears P, Wong C H
Department of Chemistry, Scripps Research Institute, La Jolla, California 92037, USA.
Cell Mol Life Sci. 1998 Mar;54(3):223-52. doi: 10.1007/s000180050146.
Just a few decades ago, the saccharides bound to glycoproteins were considered little more than an irritation. They increased the difficulty of purifying and characterizing proteins, making proteins run as several bands on gels and smearing them on columns. They were considered a nuisance and were typically cleaved away to reveal the 'important part', the protein moiety, for structural (e.g. via X-ray crystallography or nuclear magnetic resonance) and functional studies. We now realize that that the saccharide is often as important as the protein itself, and that glycosylation can have many effects on the function, structure, physical properties and targeting of a protein. There are a myriad of reviews and books on this subject, reflecting the nearly overwhelming number of articles in print discussing saccharide structures, glycoprotein processing enzymes and the biological implication of glycosylation. This review discusses, in turn, the extent and biological relevance of glycosylation; the structures observed; how glycosylated proteins are formed in vivo; the clinical relevance of glycosylation, in terms of the correlations between disease states and unusual glycosylation patterns; and, finally, the molecules, both natural and synthetic, that can be used to study the role of carbohydrates in glycoprotein structure and function or to disrupt various carbohydrate recognition processes and enzymatic reactions in the glycoprotein synthetic pathway.
就在几十年前，与糖蛋白结合的糖类还被认为只不过是一种干扰因素。它们增加了蛋白质纯化和表征的难度，使得蛋白质在凝胶上呈现出多条条带，并在柱上出现拖尾现象。它们被视为一种麻烦，通常会被切除以揭示“重要部分”，即蛋白质部分，用于结构研究（例如通过X射线晶体学或核磁共振）和功能研究。我们现在意识到，糖类往往与蛋白质本身一样重要，而且糖基化会对蛋白质的功能、结构、物理性质和靶向性产生多种影响。关于这个主题有大量的综述和书籍，这反映出印刷品中讨论糖类结构、糖蛋白加工酶以及糖基化生物学意义的文章数量几乎多得惊人。本综述依次讨论糖基化的程度和生物学相关性；观察到的结构；体内糖基化蛋白是如何形成的；糖基化的临床相关性，即疾病状态与异常糖基化模式之间的相关性；最后讨论可用于研究糖类在糖蛋白结构和功能中的作用或破坏糖蛋白合成途径中各种糖类识别过程和酶促反应的天然和合成分子。
