6MBB

Human Bfl-1 in complex with the designed peptide dF1

6MBB の概要

• エントリーDOI: 10.2210/pdb6mbb/pdb
• 分子名称: Bcl-2-related protein A1, dF1 (3 entities in total)
• 機能のキーワード: anti-apoptotic bcl-2, inhibitor, design, apoptosis
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19966.75

構造登録者

Jenson, J.M.,Keating, A.E. (登録日: 2018-08-29, 公開日: 2019-03-06, 最終更新日: 2024-11-06)

主引用文献

Frappier, V.,Jenson, J.M.,Zhou, J.,Grigoryan, G.,Keating, A.E.
Tertiary Structural Motif Sequence Statistics Enable Facile Prediction and Design of Peptides that Bind Anti-apoptotic Bfl-1 and Mcl-1.
Structure, 27:606-617.e5, 2019

PubMed Abstract: Understanding the relationship between protein sequence and structure well enough to design new proteins with desired functions is a longstanding goal in protein science. Here, we show that recurring tertiary structural motifs (TERMs) in the PDB provide rich information for protein-peptide interaction prediction and design. TERM statistics can be used to predict peptide binding energies for Bcl-2 family proteins as accurately as widely used structure-based tools. Furthermore, design using TERM energies (dTERMen) rapidly and reliably generates high-affinity peptide binders of anti-apoptotic proteins Bfl-1 and Mcl-1 with just 15%-38% sequence identity to any known native Bcl-2 family protein ligand. High-resolution structures of four designed peptides bound to their targets provide opportunities to analyze the strengths and limitations of the computational design method. Our results support dTERMen as a powerful approach that can complement existing tools for protein engineering.

PubMed: 30773399
DOI: 10.1016/j.str.2019.01.008

実験手法

X-RAY DIFFRACTION (1.59 Å)