Engineering Human Neuroglobin into a Cytochrome c-Like Protein with a Single Thioether Bond in Non-native State

Lei Chen; Hong Yuan; Xiao-Juan Wang; Lianzhi Li; Xiangshi Tan; Ying-Wu Lin

doi:10.1002/cbic.202200531

Engineering Human Neuroglobin into a Cytochrome c-Like Protein with a Single Thioether Bond in Non-native State

Chembiochem. 2022 Dec 5;23(23):e202200531. doi: 10.1002/cbic.202200531. Epub 2022 Nov 2.

Authors

Lei Chen¹, Hong Yuan², Xiao-Juan Wang¹, Lianzhi Li³, Xiangshi Tan², Ying-Wu Lin^{1

4}

Affiliations

¹ School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001, China.
² Department of Chemistry & Institute of Biomedical Science, Fudan University, Shanghai, 200433, China.
³ School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, 252059, China.
⁴ Key Lab of Protein Structure and Function of Universities in Hunan Province, University of South China, Hengyang, 421001, China.

PMID: 36217897
DOI: 10.1002/cbic.202200531

Abstract

A double mutant of human H64M/V71C neuroglobin (Ngb) was engineered, which formed a single thioether bond as that in atypical cytochrome c, whereas the heme distal Met64 was oxidized to both sulfoxide (SO-Met) and sulfone (SO₂ -Met). By contrast, no Cys-heme cross-link was formed in V71C Ngb with His64/His96 coordination, as shown by the X-ray crystal structure, which indicates that an open distal site facilitates the activation of heme iron for structural modifications.

Keywords: cross-links; crystal structures; heme proteins; non-native states; thioether bonds.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytochromes c* / genetics
Cytochromes c* / metabolism
Heme / chemistry
Humans
Neuroglobin / chemistry
Neuroglobin / metabolism
Oxidation-Reduction
Protein Engineering
Sulfides*

Substances

Cytochromes c
Heme
Neuroglobin
Sulfides