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

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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.