1HL8

CRYSTAL STRUCTURE OF THERMOTOGA MARITIMA ALPHA-FUCOSIDASE

Summary for 1HL8

• Entry DOI: 10.2210/pdb1hl8/pdb
• Related: 1HL9 1ODU
• Descriptor: PUTATIVE ALPHA-L-FUCOSIDASE (2 entities in total)
• Functional Keywords: hydrolase, glycoside hydrolase, alpha-l-fucosidase, thermostable
• Biological source: THERMOTOGA MARITIMA
• Total number of polymer chains: 2
• Total formula weight: 104630.10

Authors

Sulzenbacher, G.,Bignon, C.,Bourne, Y.,Henrissat, B. (deposition date: 2003-03-14, release date: 2004-01-15, Last modification date: 2011-07-13)

Primary citation

Sulzenbacher, G.,Bignon, C.,Nishimura, T.,Tarling, C.A.,Withers, S.G.,Henrissat, B.,Bourne, Y.
Crystal Structure of Thermotoga Maritima Alpha-L-Fucosidase. Insights Into the Catalytic Mechanism and the Molecular Basis for Fucosidosis.
J.Biol.Chem., 279:13119-, 2004

PubMed Abstract: Fucosylated glycoconjugates are involved in numerous biological events, and alpha-l-fucosidases, the enzymes responsible for their processing, are therefore of crucial importance. Deficiency in alpha-l-fucosidase activity is associated with fucosidosis, a lysosomal storage disorder characterized by rapid neurodegeneration, resulting in severe mental and motor deterioration. To gain insight into alpha-l-fucosidase function at the molecular level, we have determined the crystal structure of Thermotoga maritima alpha-l-fucosidase. This enzyme assembles as a hexamer and displays a two-domain fold, composed of a catalytic (beta/alpha)(8)-like domain and a C-terminal beta-sandwich domain. The structures of an enzyme-product complex and of a covalent glycosyl-enzyme intermediate, coupled with kinetic and mutagenesis studies, allowed us to identify the catalytic nucleophile, Asp(244), and the Brønsted acid/base, Glu(266). Because T. maritima alpha-l-fucosidase occupies a unique evolutionary position, being far more closely related to the mammalian enzymes than to any other prokaryotic homolog, a structural model of the human enzyme was built to document the structural consequences of the genetic mutations associated with fucosidosis.

PubMed: 14715651
DOI: 10.1074/JBC.M313783200

Experimental method

X-RAY DIFFRACTION (2.4 Å)