4NE9

PCSK9 in complex with LDLR peptide

4NE9 の概要

• エントリーDOI: 10.2210/pdb4ne9/pdb
• 関連するPDBエントリー: 2P4E
• 分子名称: Proprotein convertase subtilisin/kexin type 9, Low-density lipoprotein receptor, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: pcsk9, ldl receptor, autocatalytic cleavage, cholesterol metabolism, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 152361.05

構造登録者

Liu, S. (登録日: 2013-10-28, 公開日: 2014-09-10, 最終更新日: 2024-11-27)

主引用文献

Schroeder, C.I.,Swedberg, J.E.,Withka, J.M.,Rosengren, K.J.,Akcan, M.,Clayton, D.J.,Daly, N.L.,Cheneval, O.,Borzilleri, K.A.,Griffor, M.,Stock, I.,Colless, B.,Walsh, P.,Sunderland, P.,Reyes, A.,Dullea, R.,Ammirati, M.,Liu, S.,McClure, K.F.,Tu, M.,Bhattacharya, S.K.,Liras, S.,Price, D.A.,Craik, D.J.
Design and synthesis of truncated EGF-A peptides that restore LDL-R recycling in the presence of PCSK9 in vitro.
Chem.Biol., 21:284-294, 2014

PubMed Abstract: Disrupting the binding interaction between proprotein convertase (PCSK9) and the epidermal growth factor-like domain A (EGF-A domain) in the low-density lipoprotein receptor (LDL-R) is a promising strategy to promote LDL-R recycling and thereby lower circulating cholesterol levels. In this study, truncated 26 amino acid EGF-A analogs were designed and synthesized, and their structures were analyzed in solution and in complex with PCSK9. The most potent peptide had an increased binding affinity for PCSK9 (KD = 0.6 μM) compared with wild-type EGF-A (KD = 1.2 μM), and the ability to increase LDL-R recycling in the presence of PCSK9 in a cell-based assay.

PubMed: 24440079
DOI: 10.1016/j.chembiol.2013.11.014

実験手法

X-RAY DIFFRACTION (2.6 Å)