4KGA

Crystal structure of kallikrein-related peptidase 4

4KGA の概要

• エントリーDOI: 10.2210/pdb4kga/pdb
• 関連するPDBエントリー: 2bdg 2bdh 2bdi 4K1E 4K8Y 4KEL
• 分子名称: Kallikrein-4, NICKEL (II) ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: klk4, kallikrein-4, serine protease, protease, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: Q9Y5K2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48210.93

構造登録者

Ilyichova, O.V.,Swedberg, J.E.,de Veer, S.J.,Sit, K.C.,Harris, J.M.,Buckle, A.M. (登録日: 2013-04-29, 公開日: 2014-04-30, 最終更新日: 2024-11-20)

主引用文献

Riley, B.T.,Ilyichova, O.,Costa, M.G.S.,Porebski, B.T.,de Veer, S.J.,Swedberg, J.E.,Kass, I.,Harris, J.M.,Hoke, D.E.,Buckle, A.M.
Direct and indirect mechanisms of KLK4 inhibition revealed by structure and dynamics
Sci Rep, 6:35385-35385, 2016

PubMed Abstract: The kallikrein-related peptidase (KLK) family of proteases is involved in many aspects of human health and disease. One member of this family, KLK4, has been implicated in cancer development and metastasis. Understanding mechanisms of inactivation are critical to developing selective KLK4 inhibitors. We have determined the X-ray crystal structures of KLK4 in complex with both sunflower trypsin inhibitor-1 (SFTI-1) and a rationally designed SFTI-1 derivative to atomic (~1 Å) resolution, as well as with bound nickel. These structures offer a structural rationalization for the potency and selectivity of these inhibitors, and together with MD simulation and computational analysis, reveal a dynamic pathway between the metal binding exosite and the active site, providing key details of a previously proposed allosteric mode of inhibition. Collectively, this work provides insight into both direct and indirect mechanisms of inhibition for KLK4 that have broad implications for the enzymology of the serine protease superfamily, and may potentially be exploited for the design of therapeutic inhibitors.

PubMed: 27767076
DOI: 10.1038/srep35385

実験手法

X-RAY DIFFRACTION (2.32 Å)