4MWT

Crystal structure of human PPCA (trigonal crystal form 2)

4MWT の概要

• エントリーDOI: 10.2210/pdb4mwt/pdb
• 関連するPDBエントリー: 1IVY 4MWS
• 分子名称: Lysosomal protective protein, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: cathepsin a, glycoprotein, serine protease, carboxypeptidase, protective protein, n-linked glycosylation, proteolytically activated form, lysosomal enzyme, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 98561.33

構造登録者

Kolli, N.,Garman, S.C. (登録日: 2013-09-25, 公開日: 2014-03-12, 最終更新日: 2024-11-20)

主引用文献

Kolli, N.,Garman, S.C.
Proteolytic activation of human cathepsin A.
J.Biol.Chem., 289:11592-11600, 2014

PubMed Abstract: Galactosialidosis is a human lysosomal storage disease caused by deficiency in the multifunctional lysosomal protease cathepsin A (also known as protective protein/cathepsin A, PPCA, catA, HPP, and CTSA; EC 3.4.16.5). Previous structural work on the inactive precursor human cathepsin A (zymogen) led to a two-stage model for activation, where proteolysis of a 1.6-kDa excision peptide is followed by a conformational change in a blocking peptide occluding the active site. Here we present evidence for an alternate model of activation of human cathepsin A, needing only cleavage of a 3.3-kDa excision peptide to yield full enzymatic activity, with no conformational change required. We present x-ray crystallographic, mass spectrometric, amino acid sequencing, enzymatic, and cellular data to support the cleavage-only activation model. The results clarify a longstanding question about the mechanism of cathepsin A activation and point to new avenues for the design of mechanism-based inhibitors of the enzyme.

PubMed: 24599961
DOI: 10.1074/jbc.M113.524280

実験手法

X-RAY DIFFRACTION (3.85 Å)