User:Jpelusov/Fucosidase

Fucosidase
Fucosidase, or α-L-fucosidase, is an enzyme (EC 3.2.1.51) responsible for catalyzing the hydrolysis of α-L-fucosyl residues. As such, fucosidase is belongs to the enzyme category hydrolase, an enzyme that catalyzes the hydrolysis of a substrate. Fucose is a 6-deoxy sugar found ubiquitously in mammals, plants, insects, and microorganisms in various structures such as more complex oligosaccharides, glycoproteins, and lipid forming glycoconjugates. As a result, fucose (Fuc) can be associated with many important physiological processes like immune recognition, development and neural functions, to name a few. Consequently, as the fucosidase enzyme is responsible for the breakdown of Fuc, it plays a crucial biological role.

While fucosidase can be found within the many fucose-containing organisms listed above, a focus on this enzyme within microbes offers some insight into some of its many structures and functions. The reaction for fucosidase begins with the enzyme recognizing specific fucosyl linkages in glycoconjugates and oligosaccharides and binds to the substrate at its active site. Then and only then can the fucosidase enzyme catalyze the hydrolysis of glycosidic bonds linking fucose residues to the rest of the molecule, which can be referred to as an aglycone. After hydrolysis of the glycosidic bond, what remains is the newly separated fucose molecule and the aglycone. This fucose molecule then participates in several other biological pathways. The reaction can be illustrated as follows:

Fucosylated substrate + Fucosidase → Fucose + Aglycone
There have been several glycoside hydrolases reported in the Carbohydrate Active Enzymes, or CAZy, database. It is important to note that microbes generally encode for fucosidases for many GH families, resulting in many variations in the structure of fucosidase. The link below sourced from "Structure and Function of Microbial alpha-L-fucosidases: a Mini Review" by Wu et al shows the crystal structures of microbial fucosidase from the GH families GH29, GH95, GH141, and GH151 and their respective active sites.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154630/bin/ebc-67-ebc20220158-g2.jpg

These fucosidases all have catalytic domains as well as one or more "terminal β-sandwich" domains with potential carbohydrate-binding properties. Of the four GH families, GH29 fucosidases are the most characterized, with their location either being extracellular or intracellular. The majority of these GH29 fucosidases seem to have a preference for a more neutral pH. GH95, GH141, and GH151 are far less characterized and require more analysis and studies in the future.

Certain gut microbes like Bifidobacteria, B. thetaiotamicron, R. gnavus, or Akkermansia muciniphila are known to produce fucosidases that cleave fucose from host glycans (Wu et al, 2023), which indicates their importance with regards to adaptation of the gut environment by these microbes. By aiding in the degradation of fucosylated oligosaccharides, fucosidases contribute to the nutrient availability and energy harvest for the microbial community. Furthermore, fucosidases may also play a role in the pathogenecity of some microbes by degrading host glycoconjugates. In humans, deficiencies in fucosidase activity can lead to lysosomal storage disorders, as fucosidase is mainly found in the lysosome. Fucosidosis, for example, is a medical disorder brought on by the accumulation of fucose-containing compounds within lysosomes. This can lead to many serious symptoms such as developmental delay, intellectual disability, skeletal abnormalities, and even organ dysfunction. Fucosidases are also in some way involved in the processing and modification of glycoproteins, which affect cellular functions like cell adhesion, signaling, and immune response regulation. More research on fucosidase is needed to further understand their functional roles in health and disease.