6Z4R

sperm whale myoglobin mutant (H64V V64A) bearing the non-canonical amino acid 3-thienylalanine as axial heme ligand

6Z4R の概要

• エントリーDOI: 10.2210/pdb6z4r/pdb
• 分子名称: Myoglobin, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• 機能のキーワード: globin, heme protein, enzyme, metal binding protein
• 由来する生物種: Physeter macrocephalus (Sperm whale)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17870.50

構造登録者

Tinzl, M.,Hilvert, D.,Mittl, P.R.E. (登録日: 2020-05-25, 公開日: 2021-04-28, 最終更新日: 2024-01-24)

主引用文献

Pott, M.,Tinzl, M.,Hayashi, T.,Ota, Y.,Dunkelmann, D.,Mittl, P.R.E.,Hilvert, D.
Noncanonical Heme Ligands Steer Carbene Transfer Reactivity in an Artificial Metalloenzyme*.
Angew.Chem.Int.Ed.Engl., 60:15063-15068, 2021

PubMed Abstract: Changing the primary metal coordination sphere is a powerful strategy for tuning metalloprotein properties. Here we used amber stop codon suppression with engineered pyrrolysyl-tRNA synthetases, including two newly evolved enzymes, to replace the proximal histidine in myoglobin with N -methylhistidine, 5-thiazoylalanine, 4-thiazoylalanine and 3-(3-thienyl)alanine. In addition to tuning the heme redox potential over a >200 mV range, these noncanonical ligands modulate the protein's carbene transfer activity with ethyl diazoacetate. Variants with increased reduction potential proved superior for cyclopropanation and N-H insertion, whereas variants with reduced E values gave higher S-H insertion activity. Given the functional importance of histidine in many enzymes, these genetically encoded analogues could be valuable tools for probing mechanism and enabling new chemistries.

PubMed: 33880851
DOI: 10.1002/anie.202103437

実験手法

X-RAY DIFFRACTION (1.96 Å)