1N2K

Crystal structure of a covalent intermediate of endogenous human arylsulfatase A

1N2K の概要

• エントリーDOI: 10.2210/pdb1n2k/pdb
• 関連するPDBエントリー: 1N2L
• 分子名称: ARYLSULFATASE A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: hydrolase, phosphate esters hydrolysis, lysosomal enzyme, modified formylglycine, inhibition, metal ion
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52724.42

構造登録者

Chruszcz, M.,Laidler, P.,Monkiewicz, M.,Ortlund, E.,Lebioda, L.,Lewinski, K. (登録日: 2002-10-23, 公開日: 2003-12-23, 最終更新日: 2025-03-26)

主引用文献

Chruszcz, M.,Laidler, P.,Monkiewicz, M.,Ortlund, E.,Lebioda, L.,Lewinski, K.
Crystal structure of a covalent intermediate of endogenous human arylsulfatase A.
J.Inorg.Biochem., 96:386-392, 2003

PubMed Abstract: The structures of human arylsulfatase A crystals soaked in solutions containing 4-methylumbelliferyl phosphate and O-phospho-DL-tyrosine have been determined at 2.7- and 3.2-A resolution, respectively. The formylglycine in position 69, a residue crucial for catalytic activity, was unambiguously identified in both structures as forming a covalent bond to the phosphate moiety. A hydroxyl group is present at the Cbeta of residue 69 and the formation of one out of two possible stereomeric forms is strongly favoured. The structures confirm the importance of the gem-diol intermediate in the arylsulfatase's catalytic mechanism. The presence of an apparently stable covalent bond is consistent with the weak phosphatase activity observed for human arylsulfatase A. The structures of the complexes suggest that phosphate ions and phosphate esters inhibit arylsulfatase in non-covalent and covalent modes, respectively. The metal ion present in the active site of arylsulfatase A isolated from human placenta is Ca(2+) and not Mg(2+) as was found in the structure of the recombinant enzyme.

PubMed: 12888274
DOI: 10.1016/S0162-0134(03)00176-4

実験手法

X-RAY DIFFRACTION (2.75 Å)