5WL4

Crystal structure of chalcone isomerase engineered from ancestral inference (ancR3)

5WL4 の概要

• エントリーDOI: 10.2210/pdb5wl4/pdb
• 分子名称: Engineered Chalcone Isomerase ancR3, FORMIC ACID (3 entities in total)
• 機能のキーワード: chalcone isomerase, naringenin, flavanone, isomerase
• 由来する生物種: unidentified
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95988.72

構造登録者

Burke, J.R.,Kaltenbach, M.,Tawfik, D.S.,Noel, J.P. (登録日: 2017-07-25, 公開日: 2018-05-09, 最終更新日: 2023-10-04)

主引用文献

Kaltenbach, M.,Burke, J.R.,Dindo, M.,Pabis, A.,Munsberg, F.S.,Rabin, A.,Kamerlin, S.C.L.,Noel, J.P.,Tawfik, D.S.
Evolution of chalcone isomerase from a noncatalytic ancestor.
Nat. Chem. Biol., 14:548-555, 2018

PubMed Abstract: The emergence of catalysis in a noncatalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a nonenzymatic ancestor related to the widely distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs). Ancestral inference supported the evolution of CHI from a protein lacking isomerase activity. Further, we identified four alternative founder mutations, i.e., mutations that individually instated activity, including a mutation that is not phylogenetically traceable. Despite strong epistasis in other cases of protein evolution, CHI's laboratory reconstructed mutational trajectory shows weak epistasis. Thus, enantioselective CHI activity could readily emerge despite a catalytically inactive starting point. Accordingly, X-ray crystallography, NMR, and molecular dynamics simulations reveal reshaping of the active site toward a productive substrate-binding mode and repositioning of the catalytic arginine that was inherited from the ancestral fatty-acid binding proteins.

PubMed: 29686356
DOI: 10.1038/s41589-018-0042-3

実験手法

X-RAY DIFFRACTION (2 Å)