6WGB

Crystal structure of the fab portion of dupilumab

6WGB の概要

• エントリーDOI: 10.2210/pdb6wgb/pdb
• 分子名称: Dupilumab Fab heavy chain, Dupilumab Fab light chain (3 entities in total)
• 機能のキーワード: dupilumab, hil4r, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 98551.80

構造登録者

Druzina, Z.,Atwell, S.,Pustilnik, A.,Antonysamy, S.,Ho, C.,Lieu, R.,Hendle, J.,Benach, J.,Wang, J. (登録日: 2020-04-05, 公開日: 2020-09-16, 最終更新日: 2024-11-20)

主引用文献

Lieu, R.,Antonysamy, S.,Druzina, Z.,Ho, C.,Kang, N.R.,Pustilnik, A.,Wang, J.,Atwell, S.
Rapid and robust antibody Fab fragment crystallization utilizing edge-to-edge beta-sheet packing.
Plos One, 15:e0232311-e0232311, 2020

PubMed Abstract: Antibody therapeutics are one of the most important classes of drugs. Antibody structures have become an integral part of predicting the behavior of potential therapeutics, either directly or as the basis of modeling. Structures of Fab:antigen complexes have even greater value. While the crystallization and structure determination of Fabs is easy relative to many other protein classes, especially membrane proteins, broad screening and optimization of crystalline hits is still necessary. Through a comprehensive review of rabbit Fab crystal contacts and their incompatibility with human Fabs, we identified a small secondary structural element from the rabbit light chain constant domain potentially responsible for hindering the crystallization of human Fabs. Upon replacing the human kappa constant domain FG loop (HQGLSSP) with the two residue shorter rabbit loop (QGTTS), we dramatically improved the crystallization of human Fabs and Fab:antigen complexes. Our design, which we call "Crystal Kappa", enables rapid crystallization of human fabs and fab complexes in a broad range of conditions, with less material in smaller screens or from dilute solutions.

PubMed: 32915778
DOI: 10.1371/journal.pone.0232311

実験手法

X-RAY DIFFRACTION (1.99 Å)