4MSL

Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with AF40431

4MSL の概要

• エントリーDOI: 10.2210/pdb4msl/pdb
• 関連するPDBエントリー: 3F6K
• 分子名称: Sortilin, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: prongf, alzheimer's disease, beta-propeller, asp-box repeat, vps10p domain, 10cc domain, receptor sorting, peptide binding, protein binding, membrane, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 79639.68

構造登録者

Andersen, J.L.,Strandbygaard, D.,Thirup, S. (登録日: 2013-09-18, 公開日: 2014-02-12, 最終更新日: 2024-11-27)

主引用文献

Andersen, J.L.,Schrder, T.J.,Christensen, S.,Strandbygard, D.,Pallesen, L.T.,Garcia-Alai, M.M.,Lindberg, S.,Langgard, M.,Eskildsen, J.C.,David, L.,Tagmose, L.,Simonsen, K.B.,Maltas, P.J.,Rnn, L.C.,de Jong, I.E.,Malik, I.J.,Egebjerg, J.,Karlsson, J.J.,Uppalanchi, S.,Sakumudi, D.R.,Eradi, P.,Watson, S.P.,Thirup, S.
Identification of the first small-molecule ligand of the neuronal receptor sortilin and structure determination of the receptor-ligand complex.
Acta Crystallogr.,Sect.D, 70:451-460, 2014

PubMed Abstract: Sortilin is a type I membrane glycoprotein belonging to the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors and is most abundantly expressed in the central nervous system. Sortilin has emerged as a key player in the regulation of neuronal viability and has been implicated as a possible therapeutic target in a range of disorders. Here, the identification of AF40431, the first reported small-molecule ligand of sortilin, is reported. Crystals of the sortilin-AF40431 complex were obtained by co-crystallization and the structure of the complex was solved to 2.7 Å resolution. AF40431 is bound in the neurotensin-binding site of sortilin, with the leucine moiety of AF40431 mimicking the binding mode of the C-terminal leucine of neurotensin and the 4-methylumbelliferone moiety of AF40431 forming π-stacking with a phenylalanine.

PubMed: 24531479
DOI: 10.1107/S1399004713030149

実験手法

X-RAY DIFFRACTION (2.7 Å)