1FMI

CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE

1FMI の概要

• エントリーDOI: 10.2210/pdb1fmi/pdb
• 分子名称: ENDOPLASMIC RETICULUM ALPHA-MANNOSIDASE I, CALCIUM ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: alpha-alpha7 barrel, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Single-pass type II membrane protein: Q9UKM7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52911.96

構造登録者

Vallee, F.,Karaveg, K.,Herscovics, A.,Moremen, K.W.,Howell, P.L. (登録日: 2000-08-17, 公開日: 2001-01-17, 最終更新日: 2024-11-20)

主引用文献

Vallee, F.,Karaveg, K.,Herscovics, A.,Moremen, K.W.,Howell, P.L.
Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases.
J.Biol.Chem., 275:41287-41298, 2000

PubMed Abstract: Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER alpha-mannosidase I) is a critical enzyme in the maturation of N-linked oligosaccharides and ER-associated degradation. Trimming of a single mannose residue acts as a signal to target misfolded glycoproteins for degradation by the proteasome. Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin. Both inhibitors bind to the protein at the bottom of the active-site cavity, with the essential calcium ion coordinating the O-2' and O-3' hydroxyls and stabilizing the six-membered rings of both inhibitors in a (1)C(4) conformation. This is the first direct evidence of the role of the calcium ion. The lack of major conformational changes upon inhibitor binding and structural comparisons with the yeast alpha1, 2-mannosidase enzyme-product complex suggest that this class of inverting enzymes has a novel catalytic mechanism. The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases.

PubMed: 10995765
DOI: 10.1074/jbc.M006927200

実験手法

X-RAY DIFFRACTION (1.9 Å)