9DBC

Mn-Bound Structure of Computationally Designed Homotrimer Tet4

9DBC の概要

• エントリーDOI: 10.2210/pdb9dbc/pdb
• 分子名称: Computationally Designed Tet4, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: metalloprotein, computational design, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12616.55

構造登録者

Hoffnagle, A.M.,Tezcan, F.A. (登録日: 2024-08-23, 公開日: 2025-08-06)

主引用文献

Hoffnagle, A.M.,Srisantitham, S.,Neeley, M.,Tsai, C.Y.,Tezcan, F.A.
A De Novo Designed Protein with Versatile Metal Binding and Tunable Hydrolytic Activity.
Biochemistry, 2025

PubMed Abstract: Metalloenzyme superfamilies achieve diverse functions within a shared structural framework, and similar functional variety may be achievable in designed proteins. We have previously reported a computational approach that enables the design of symmetric protein assemblies around metal centers with predefined coordination geometries. Here, we demonstrate that an artificial protein trimer, termed Tet4, whose structure was designed around an idealized tetrahedral His/HO-Zn coordination motif, enables the high-affinity binding of several other divalent first-row transition metal ions in the same geometry as for Zn. We then follow the proposed evolutionary path of a natural metalloenzyme superfamily by engineering a pseudosymmetric, single-chain variant of Tet4, scTet4. scTet4 allows us to introduce asymmetric point mutations that influence the catalytic properties of the metal center. We also demonstrate that we can further tune the enzymatic activity of Tet4 by designing a substrate pocket that improves Zn-Tet4's affinity for a hydrolysis substrate, 4-methylumbelliferyl acetate.

PubMed: 40700614
DOI: 10.1021/acs.biochem.5c00259

実験手法

X-RAY DIFFRACTION (2.3 Å)