9EMQ

Crystal Structure of DC-SIGN in complex with AL86

これはPDB形式変換不可エントリーです。

9EMQ の概要

• エントリーDOI: 10.2210/pdb9emq/pdb
• 分子名称: DC-SIGN, CRD domain, CALCIUM ION, (2~{R},3~{S},4~{R},5~{S},6~{S})-2-(hydroxymethyl)-5-(4-phenyl-1,2,3-triazol-1-yl)-6-[[(3~{S})-piperidin-3-yl]methoxy]oxane-3,4-diol, ... (4 entities in total)
• 機能のキーワード: glyomimetic, dc-sign, sugar binding 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: 18684.74

構造登録者

Jakob, R.P.,Cramer, J.,Maier, T. (登録日: 2024-03-09, 公開日: 2024-11-13)

主引用文献

Nemli, D.D.,Jiang, X.,Jakob, R.P.,Gloder, L.M.,Schwardt, O.,Rabbani, S.,Maier, T.,Ernst, B.,Cramer, J.
Thermodynamics-Guided Design Reveals a Cooperative Hydrogen Bond in DC-SIGN-targeted Glycomimetics.
J.Med.Chem., 67:13813-13828, 2024

PubMed Abstract: Due to the shallow and hydrophilic binding sites of carbohydrate-binding proteins, the design of glycomimetics is often complicated by high desolvation costs as well as competition with solvent. Therefore, a careful optimization of interaction vectors and ligand properties is required in the design and optimization of glycomimetics. Here, we employ thermodynamics-guided design to optimize mannose-based glycomimetics targeting the human C-type lectin receptor dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin (DC-SIGN), a pathogenic host factor in viral infections. By exploring ligand rigidification and hydrogen bond engineering, a monovalent glycomimetic with an unprecedented affinity for DC-SIGN in the low μM range was discovered. A matched molecular pair analysis based on microcalorimetric data revealed a stereospecific hydrogen bond interaction with Glu358/Ser360 as the origin of this cooperative and enthalpically dominated interaction. This detailed insight into the binding mechanism paves the way for an improvement of monovalent glycomimetics targeting DC-SIGN.

PubMed: 38771131
DOI: 10.1021/acs.jmedchem.4c00623

実験手法

X-RAY DIFFRACTION (1.8 Å)