5F1K

human CD38 in complex with nanobody MU1053

5F1K の概要

• エントリーDOI: 10.2210/pdb5f1k/pdb
• 分子名称: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1, nanobody MU1053 (3 entities in total)
• 機能のキーワード: cd38, adp-ribosyl cyclase, cyclic adp-ribose, x-crystallography, calcium signaling, nanobody, mu1053, hydrolase-immune system complex, hydrolase/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Membrane; Single-pass type II membrane protein: P28907
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93513.17

構造登録者

Zhang, H.,Hao, Q. (登録日: 2015-11-30, 公開日: 2016-06-15, 最終更新日: 2024-10-30)

主引用文献

Li, T.,Qi, S.,Unger, M.,Hou, Y.N.,Deng, Q.W.,Liu, J.,Lam, C.M.,Wang, X.W.,Xin, D.,Zhang, P.,Koch-Nolte, F.,Hao, Q.,Zhang, H.,Lee, H.C.,Zhao, Y.J.
Immuno-targeting the multifunctional CD38 using nanobody
Sci Rep, 6:27055-27055, 2016

PubMed Abstract: CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10(-11) molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma.

PubMed: 27251573
DOI: 10.1038/srep27055

実験手法

X-RAY DIFFRACTION (2.3 Å)