Alpha_L_fucos

Alpha-L-fucosidase

• SMART accession number: SM00812
• Description: O-Glycosyl hydrolases (EC 3.2.1.-) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site PUBMED:. Because the fold of proteins is better conserved than their sequences, some of the families can be grouped in 'clans'. Family 29 encompasses alpha-L-fucosidases, which is a lysosomal enzyme responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins. Deficiency of alpha-L-fucosidase results in the lysosomal storage disease fucosidosis.
• Interpro abstract (IPR000933):

  O-Glycosyl hydrolases (EC 3.2.1.) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [(PUBMED:7624375), (PUBMED:8535779)]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site.

  Family 29 encompasses alpha-L-fucosidases (EC 3.2.1.51) [(PUBMED:2482732)], which is a lysosomal enzyme responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins. Alpha-L-fucosidase is responsible for hydrolysing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.

  Fucosylated glycoconjugates are involved in numerous biological events, making alpha-l-fucosidases, the enzymes responsible for their processing, critically important. Deficiency in alpha-l-fucosidase activity is associated with fucosidosis, a lysosomal storage disorder characterised by rapid neurodegeneration, resulting in severe mental and motor deterioration [(PUBMED:14715651)]. The enzyme is a hexamer and displays a two-domain fold, composed of a catalytic (beta/alpha)(8)-like domain and a C-terminal beta-sandwich domain [(PUBMED:14715651)].

  Drosophila melanogaster spermatozoa contains an alpha-l-fucosidase that might be involved in fertilisation by interacting with alpha-l-fucose residues on the micropyle of the eggshell [(PUBMED:18556148)]. In human sperm, membrane-associated alpha-l-fucosidase is stable for extended periods of time, which is made possible by membrane domains and compartmentalisation. These help preserve protein integrity [(PUBMED:18522672)].

• GO process: carbohydrate metabolic process (GO:0005975)
• GO function: alpha-L-fucosidase activity (GO:0004560)

There are 849 Alpha_L_fucos domains in 849 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: metabolism

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Davies G, Henrissat B
• Structures and mechanisms of glycosyl hydrolases.
• Structure. 1995; 3: 853-9

The wealth of information provided by the recent structure determinations of many different glycosyl hydrolases shows that the substrate specificity and the mode of action of these enzymes are governed by exquisite details of their three-dimensional structures rather than by their global fold.

• Henrissat B, Callebaut I, Fabrega S, Lehn P, Mornon JP, Davies G
• Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases.
• Proc Natl Acad Sci U S A. 1995; 92: 7090-4

The regions surrounding the catalytic amino acids previously identified in a few "retaining" O-glycosyl hydrolases (EC 3.2.1) have been analyzed by hydrophobic cluster analysis and have been used to define sequence motifs. These motifs have been found in more than 150 glycosyl hydrolase sequences representing at least eight established protein families that act on a large variety of substrates. This allows the localization and the precise role of the catalytic residues (nucleophile and acid catalyst) to be predicted for each of these enzymes, including several lysosomal glycosidases. An identical arrangement of the catalytic nucleophile was also found for S-glycosyl hydrolases (myrosinases; EC 3.2.3.1) for which the acid catalyst is lacking. A (beta/alpha)8 barrel structure has been reported for two of the eight families of proteins that have been grouped. It is suggested that the six other families also share this fold at their catalytic domain. These enzymes illustrate how evolutionary events led to a wide diversification of substrate specificity with a similar disposition of identical catalytic residues onto the same ancestral (beta/alpha)8 barrel structure.

• Fisher KJ, Aronson NN Jr
• Isolation and sequence analysis of a cDNA encoding rat liver alpha-L-fucosidase.
• Biochem J. 1989; 264: 695-701

cDNA clones for alpha-L-fucosidase were isolated from a rat liver lambda gt11 expression library by using both monospecific polyclonal antibodies against the affinity-purified enzyme and biotinylated rat liver fucosidase cDNA sequences as probes. The largest clone, lambda FC9, contained a 1522 bp full-length cDNA insert (FC9) that encoded the 434-amino acid-residue subunit (Mr 50439) of rat liver alpha-L-fucosidase. A putative signal peptide 28 amino acid residues in length preceded the sequence for the mature protein. In addition, FC9 specified for 11 nucleotide residues of 5' untranslated sequence, 78 nucleotide residues of 3' untranslated sequence and a poly(A) tail. The deduced amino acid sequence from FC9 in conjunction with the experimentally determined N-terminus of the mature enzyme suggested that rat liver fucosidase did not contain a pro-segment. However, there was the possibility of limited N-terminal processing (one to five amino acid residues) having occurred after removal of the predicted signal peptide. Amino acid sequences deduced from FC9 were co-linear with amino acid sequences measured at the N-terminus of purified fucosidase and on two of its CNBr-cleavage peptides. An unusual aspect of rat liver alpha-L-fucosidase protein structure obtained from the FC9 data was its high content of tryptophan (6%). The coding sequence from FC9 showed 82% sequence identity with that from a previously reported incomplete human fucosidase sequence [O'Brien, Willems, Fukushima, de Wet, Darby, DiCioccio, Fowler & Shows, (1987) Enzyme 38, 45-53].

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
50.00	map00511	N-Glycan degradation
50.00	map01032	Glycan structures - degradation

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with Alpha_L_fucos domain which could be assigned to a KEGG orthologous group, and not all proteins containing Alpha_L_fucos domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of Alpha_L_fucos domains in PDB

PDB code	Title
1hl8	Crystal structure of thermotoga maritima alpha-fucosidase
1hl9	Crystal structure of thermotoga maritima alpha-fucosidase in complex with a mechanism based inhibitor
1odu	Crystal structure of thermotoga maritima alpha-fucosidase in complex with fucose
3eyp	Crystal structure of putative alpha-l-fucosidase from bacteroides thetaiotaomicron
3gza	Crystal structure of putative alpha-l-fucosidase (np_812709.1) from bacteroides thetaiotaomicron vpi-5482 at 1.60 a resolution

Links (links to other resources describing this domain)

• PFAM: Alpha_L_fucos
• INTERPRO: IPR000933