9RM3

Crystal structure of human CD22 Ig domains 1-3 in complex with modified sialoside 17

これはPDB形式変換不可エントリーです。

9RM3 の概要

• エントリーDOI: 10.2210/pdb9rm3/pdb
• 分子名称: B-cell receptor CD22, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: siglec, sialic acid, b cell, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 152927.08

構造登録者

Ereno-Orbea, J.,Sicard, T.,Julien, J.-P. (登録日: 2025-06-17, 公開日: 2026-01-28)

主引用文献

Ereno-Orbea, J.,Pang, L.,Sicard, T.,Nycholat, C.,Cui, H.,Borovsky, D.,Franconetti, A.,Jimenez-Barbero, J.,Paulson, J.C.,Julien, J.P.
Molecular Insights into the Engagement of High-Affinity Sialylated Ligands to Human CD22.
Jacs Au, 5:5524-5537, 2025

PubMed Abstract: CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that maintains a baseline level of B cell inhibition. Its function and restricted expression in B cells make CD22 a validated target in therapies against dysregulated B cells, which cause cancer and autoimmune diseases. High-affinity sialic acid-based ligands capable of competing with natural ligands to bind CD22 represent a promising therapeutic opportunity. Here, we describe the design and synthesis of a sialoside library constructed by chemical modifications on carbon C2 of 9--biphenylcarboxamide Neu5Ac (Neu5Ac) or 9--m-phenoxybenzamide Neu5FAc (Neu5FAc) scaffold using a copper-(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Subsequent analysis of binding to human CD22 using competitive binding assays and isothermal titration calorimetry reveals that addition of noncarbohydrate substituents at C2 and C9 can improve the affinity toward CD22 from high micromolar to submicromolar values. We describe the molecular basis of this affinity improvement for three of the newly synthesized compounds by solving cocrystal structures in complex with CD22. These findings contribute to our understanding of the affinity increase of chemically modified Neu5Ac toward CD22, providing the molecular basis for further compound design of sialic acid-based molecules with potential therapeutic relevance.

PubMed: 41311955
DOI: 10.1021/jacsau.5c01013

実験手法

X-RAY DIFFRACTION (2.857 Å)