Glycoside Hydrolase Family 29

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• Author: ^^^Gerlind Suzlenbacher^^^
• Responsible Curator: ^^^Steve Withers^^^

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Glycoside Hydrolase Family GH 29
Clan	none
Mechanism	retaining
Active site residues	known
CAZy DB link
http://www.cazy.org/fam/GH29.html

Substrate specificities

The glycoside hydrolases of this family are exo-acting α-fucosidases from archaeal, bacterial and eukaryotic origin. No other activities have been observed for GH29 family members. So fare the only other CAZY family containing α-fucosidases is family GH95. The human enzyme FucA1 is of medical interest because its deficiency leads to fucosidosis, an autosomal recessive lysosomal storage disease [1].

Kinetics and Mechanism

GH29 α-fucosidases are retaining enzymes following a classical Koshland double-displacement mechanism, as first proposed in 1987 for human liver α-fucosidase via burst kinetics experiments and using methanol as an alternative glycone acceptor to produce methyl-α-L-fucoside [2]. This has been further confirmed by ¹H NMR monitoring of the reaction catalyzed by a α-L-fucosidase from Thermus sp. [3], and a α-L-fucosidase from the marine mollusc Pecten maximus[4], as well as by COSY and ¹H-¹³C NMR spectroscopy analysis of the interglycosidic linkage of disaccharides formed by the transglycosylation action of Sulfolobus solfataricus α-L-fucosidase [5]. GH95 α-fucosidases, in contrast, operate with inversion of the anomeric configuration.

Catalytic Residues

           Normal.dotm   0   0   1   152   872   AFMB   7   1   1070   12.0               0   false      21      18 pt   18 pt   0   0      false   false   false                                    The catalytic nucleophile in GH29 was first identified in the Sulfolobus solfataricus α-L-fucosidase as Asp242 in the sequence VYFDWWI via chemical rescue of an inactive mutant with sodium azide (Cobucci-Ponzano, B., Trincone, A., Giordano, A., Rossi, M., and Moracci, M. Biochemistry 42, 9525–9531).  Concomitantly the catalytic nucleophile of Thermotoga maritima α-L-fucosidase was confirmed to be Asp224 in the sequence LWNDMGW through trapping of the 2-deoxy-2-fluorofucosyl-enzyme intermediate and subsequent peptide mapping via LC-MS/MS technologies, as well as by chemical rescue of an inactive mutant. The trapping of the 2-deoxy-2-fluorofucosyl-enzyme intermediate in Thermotoga maritima was corroborated by crystallographic studies.   

Three-dimensional structures

Content is to be added here.

Family Firsts

First sterochemistry determination

Cite some reference here, with a short (1-2 sentence) explanation [6].

First catalytic nucleophile identification

Cite some reference here, with a short (1-2 sentence) explanation [7].

First general acid/base residue identification

Cite some reference here, with a short (1-2 sentence) explanation [8].

First 3-D structure

Cite some reference here, with a short (1-2 sentence) explanation [3].

References

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