5N70

CRYSTAL STRUCTURE OF MATURE CATHEPSIN D FROM THE TICK IXODES RICINUS (IRCD1) IN COMPLEX WITH THE N-TERMINAL OCTAPEPTIDE OF THE PROPEPTID

5N70 の概要

• エントリーDOI: 10.2210/pdb5n70/pdb
• 分子名称: Putative cathepsin d, ALA-PHE-ARG-ILE-PRO-LEU-THR-ARG (3 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Ixodes ricinus (castor bean tick); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38590.30

構造登録者

Brynda, J.,Hanova, I.,Hobizalova, R.,Mares, M. (登録日: 2017-02-17, 公開日: 2017-12-27, 最終更新日: 2024-11-20)

主引用文献

Hanova, I.,Brynda, J.,Houstecka, R.,Alam, N.,Sojka, D.,Kopacek, P.,Maresova, L.,Vondrasek, J.,Horn, M.,Schueler-Furman, O.,Mares, M.
Novel Structural Mechanism of Allosteric Regulation of Aspartic Peptidases via an Evolutionarily Conserved Exosite.
Cell Chem Biol, 25:318-329.e4, 2018

PubMed Abstract: Pepsin-family aspartic peptidases are biosynthesized as inactive zymogens in which the propeptide blocks the active site until its proteolytic removal upon enzyme activation. Here, we describe a novel dual regulatory function for the propeptide using a set of crystal structures of the parasite cathepsin D IrCD1. In the IrCD1 zymogen, intramolecular autoinhibition by the intact propeptide is mediated by an evolutionarily conserved exosite on the enzyme core. After activation, the mature enzyme employs the same exosite to rebind a small fragment derived from the cleaved propeptide. This fragment functions as an effective natural inhibitor of mature IrCD1 that operates in a pH-dependent manner through a unique allosteric inhibition mechanism. The study uncovers the propeptide-binding exosite as a target for the regulation of pepsin-family aspartic peptidases and defines the structural requirements for exosite inhibition.

PubMed: 29396291
DOI: 10.1016/j.chembiol.2018.01.001

実験手法

X-RAY DIFFRACTION (1.81 Å)