Understanding the structure and function of an important human metabolic enzyme.

各种类型的碳水化合物或糖在自然界中无处不在，在我们的细胞中起着许多重要的作用。碳水化合物可以存在于长链中，由一种或多种单糖组成，这就是我们摄取的食物如何将能量储存在细胞中，为什么木材很坚固，并负责将我们的细胞粘在一起的分子胶。在规模的另一端，单个或小群的特殊单糖可以附加到其他生物分子上，如蛋白质和脂质，在那里它们协调细胞过程，如细胞间和细胞内信号传导，以及防御病原体。碳水化合物的结构和序列是复杂和高度可变的，但与DNA不同的是，碳水化合物没有可以读取的遗传密码来确定它应该如何存在。相反，碳水化合物的结构和序列仅由合成、降解和修饰碳水化合物分子的酶来定义。因此，人体碳水化合物加工酶是至关重要的，但对它们的研究较少，酶的特征也很差。对于那些被充分理解的，这些酶的功能障碍或错误调节与诸如癌症、代谢和炎症性疾病等疾病密切相关。其中一种人类代谢酶是n -乙酰氨基葡萄糖-6-磷酸脱乙酰酶，简称NagA。NagA催化n -乙酰氨基-6-磷酸去乙酰化生成氨基-6-磷酸。人类NagA的结构已经得到解决，发现它具有混杂的底物范围。尽管我们对人类的NagA知之甚少，但对细菌的同源物却有更充分的了解。有趣的是，细菌的NagA并没有表现出相同的底物混杂，这表明人类的NagA进化出这种功能是有特殊原因的。对这种酶进行表征的工作很少，其生理作用也不为人所知。目前，我们假设这种酶起到了看门人的作用，以确保没有错误的基团能够进入代谢途径，这可能会对许多下游过程产生根本性的影响。人体碳水化合物处理酶发挥着重要的生物功能，当它们不能正常工作时，就会导致癌症、代谢和炎症紊乱等疾病。从分子水平上了解这种人体代谢酶，首先推断它是如何工作的，然后了解它的生物学功能，对未来的健康和疾病有重要的影响。

Various types of carbohydrates, or sugars, are ubiquitous throughout nature and perform a number of important functions in our cells. Carbohydrates can exist in long chains, composed of one or more types of monosaccharides, which is how energy is stored in cells from the food we ingest, why wood is strong, and is responsible for the molecular glue that sticks our cells together. At the other end of the scale, single or small groups of specialized monosaccharides can be appended to other biomolecules such as proteins and lipids, where they work to coordinate cell processes such as inter- and intra-cellular signalling, and defence against pathogens. The structure and sequence of carbohydrates are complex and highly variable, but unlike DNA there is no genetic code that can be read to determine how it should exist. Instead, carbohydrate structure and sequence are defined only by the enzymes that synthesize, degrade and modify the carbohydrate molecules.Human carbohydrate processing enzymes are therefore vitally important, but they are less well studied and the enzymes are poorly characterised. For those that are well understood, the malfunction or mis-regulation of such enzymes is strongly associated with diseases such as cancer and metabolic and inflammatory disorders. One such human metabolic enzyme that is poorly understood is N-acetylglucosamine-6-phosphate deacetylase, or NagA. NagA catalyses the deacetylation of N-acetylglucosamine-6-phosphate to produce glucosamine-6-phosphate. The structure of human NagA has been solved and it was found to have a promiscuous substrate scope. Although the human NagA is poorly understood, there are bacterial homologues which are more well characterised. Interestingly, bacterial NagA does not show the same substrate promiscuity, suggesting that human NagA has evolved this function for a particular reason.Little work has been done to characterise the enzyme, and its physiological role is not understood. At the moment we hypothesize this enzyme acts as a gate-keeper to ensure no erroneous groups can make their way into metabolic pathways, which could have fundamental consequences in a number of downstream processes. Human carbohydrate processing enzymes perform important biological functions and when they fail to work properly are implicated in diseases including cancer, and metabolic and inflammatory disorders. Understanding this human metabolic enzyme at the molecular level, by firstly deducing how it works, and then understanding its biological function, could have an important impact on the health and disease in the future.