5K1V

Crystal structure of Endoplasmic Reticulum aminopeptidase 2 (ERAP2) in complex with a diaminobenzoic acid derivative ligand.

5K1V の概要

• エントリーDOI: 10.2210/pdb5k1v/pdb
• 分子名称: Endoplasmic reticulum aminopeptidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: endoplasmic reticulum aminopeptidase, hydrolase, zinc-binding metallopeptidase, diaminobenzoic acid derivative
• 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: 228025.33

構造登録者

Saridakis, E.,Papakyriakou, A.,Giastas, P.,Mpakali, A.,Mavridis, I.M.,Stratikos, E. (登録日: 2016-05-18, 公開日: 2017-03-29, 最終更新日: 2024-10-09)

主引用文献

Mpakali, A.,Giastas, P.,Deprez-Poulain, R.,Papakyriakou, A.,Koumantou, D.,Gealageas, R.,Tsoukalidou, S.,Vourloumis, D.,Mavridis, I.M.,Stratikos, E.,Saridakis, E.
Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency.
ACS Med Chem Lett, 8:333-337, 2017

PubMed Abstract: Endoplasmic reticulum aminopeptidase 2 assists with the generation of antigenic peptides for presentation onto Major Histocompatibility Class I molecules in humans. Recent evidence has suggested that the activity of ERAP2 may contribute to the generation of autoimmunity, thus making ERAP2 a possible pharmacological target for the regulation of adaptive immune responses. To better understand the structural elements of inhibitors that govern their binding affinity to the ERAP2 active site, we cocrystallized ERAP2 with a medium activity 3,4-diaminobenzoic acid inhibitor and a poorly active hydroxamic acid derivative. Comparison of these two crystal structures with a previously solved structure of ERAP2 in complex with a potent phosphinic pseudopeptide inhibitor suggests that engaging the substrate N-terminus recognition properties of the active site is crucial for inhibitor binding even in the absence of a potent zinc-binding group. Proper utilization of all five major pharmacophores is necessary, however, to optimize inhibitor potency.

PubMed: 28337326
DOI: 10.1021/acsmedchemlett.6b00505

実験手法

X-RAY DIFFRACTION (2.897 Å)