3V1C

Crystal structure of de novo designed MID1-zinc

3V1C の概要

• エントリーDOI: 10.2210/pdb3v1c/pdb
• 関連するPDBエントリー: 1YZM 3V1A 3V1B 3V1D 3V1E 3V1F
• 分子名称: Computational design, MID1-zinc, ZINC ION, L(+)-TARTARIC ACID, ... (5 entities in total)
• 機能のキーワード: helix-turn-helix, metal binding, homodimer, metal binding protein, hydrolase, de novo protein
• 由来する生物種: ARTIFICIAL GENE
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 11279.14

構造登録者

Der, B.S.,Machius, M.,Miley, M.J.,Kuhlman, B. (登録日: 2011-12-09, 公開日: 2012-01-11, 最終更新日: 2023-09-13)

主引用文献

Der, B.S.,Machius, M.,Miley, M.J.,Mills, J.L.,Szyperski, T.,Kuhlman, B.
Metal-mediated affinity and orientation specificity in a computationally designed protein homodimer.
J.Am.Chem.Soc., 134:375-385, 2012

PubMed Abstract: Computationally designing protein-protein interactions with high affinity and desired orientation is a challenging task. Incorporating metal-binding sites at the target interface may be one approach for increasing affinity and specifying the binding mode, thereby improving robustness of designed interactions for use as tools in basic research as well as in applications from biotechnology to medicine. Here we describe a Rosetta-based approach for the rational design of a protein monomer to form a zinc-mediated, symmetric homodimer. Our metal interface design, named MID1 (NESG target ID OR37), forms a tight dimer in the presence of zinc (MID1-zinc) with a dissociation constant <30 nM. Without zinc the dissociation constant is 4 μM. The crystal structure of MID1-zinc shows good overall agreement with the computational model, but only three out of four designed histidines coordinate zinc. However, a histidine-to-glutamate point mutation resulted in four-coordination of zinc, and the resulting metal binding site and dimer orientation closely matches the computational model (Cα rmsd = 1.4 Å).

PubMed: 22092237
DOI: 10.1021/ja208015j

実験手法

X-RAY DIFFRACTION (1.129 Å)