7DHA

crystal structure of CD38 in complex with daratumumab

7DHA の概要

• エントリーDOI: 10.2210/pdb7dha/pdb
• 分子名称: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1, Light chain, Heavy Chain, ... (4 entities in total)
• 機能のキーワード: cd38, antibody, daratumumab, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 79130.75

構造登録者

Lee, H.T.,Heo, Y.S. (登録日: 2020-11-13, 公開日: 2021-09-22, 最終更新日: 2024-11-13)

主引用文献

Lee, H.T.,Kim, Y.,Park, U.B.,Jeong, T.J.,Lee, S.H.,Heo, Y.S.
Crystal structure of CD38 in complex with daratumumab, a first-in-class anti-CD38 antibody drug for treating multiple myeloma.
Biochem.Biophys.Res.Commun., 536:26-31, 2021

PubMed Abstract: Multiple myeloma is a blood cancer characterized by the plasma cell malignancy in the bone marrow, resulting in the destruction of bone tissue. Recently, the US FDA approved two antibody drugs for the treatment of multiple myeloma, daratumumab and isatuximab, targeting CD38, a type II transmembrane glycoprotein highly expressed in plasma cells and multiple myeloma cells. Here, we report the crystal structure of CD38 in complex with the Fab fragment of daratumumab, providing its exact epitope on CD38 and the structural insights into the mechanism of action of the antibody drug. Daratumumab binds to a specific discontinuous region on CD38 that includes residues located opposite to the active site of CD38. All the six complementarity determining regions of daratumumab are involved in the CD38 interaction. The epitopes of daratumumab and isatuximab do not overlap at all and their bindings to CD38 induce different structural changes within the CD38 protein. This structural study can facilitate the design of improved biologics or effective combination therapies for the treatment of multiple myeloma.

PubMed: 33360095
DOI: 10.1016/j.bbrc.2020.12.048

実験手法

X-RAY DIFFRACTION (2.55 Å)