1HL9

CRYSTAL STRUCTURE OF THERMOTOGA MARITIMA ALPHA-FUCOSIDASE IN COMPLEX WITH A MECHANISM BASED INHIBITOR

1HL9 の概要

• エントリーDOI: 10.2210/pdb1hl9/pdb
• 関連するPDBエントリー: 1HL8
• 分子名称: PUTATIVE ALPHA-L-FUCOSIDASE, 2-deoxy-2-fluoro-beta-L-fucopyranose (3 entities in total)
• 機能のキーワード: hydrolase, glycoside hydrolase, alpha-l-fucosidase, glycosyl-enzyme intermediate, thermostable
• 由来する生物種: THERMOTOGA MARITIMA
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 104962.40

構造登録者

Sulzenbacher, G.,Bignon, C.,Bourne, Y.,Henrissat, B. (登録日: 2003-03-14, 公開日: 2004-02-05, 最終更新日: 2023-12-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.25 Å)