Regulating the Heme Active Site by Covalent Modifications: Two Case Studies of Myoglobin

Using myoglobin (Mb) as a model protein, we herein developed a facial approach to modifying the heme active site. A cavity was first generated in the heme distal site by F46 C mutation, and the thiol group of Cys46 was then used for covalently linked to exogenous ligands, 1H‐1,2,4‐triazole‐3‐thiol a...

Full description

Saved in:
Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2024-02, Vol.25 (3), p.e202300678-n/a
Main Authors: Chen, Ze‐Yuan, Yuan, Hong, Wang, Huamin, Sun, Li‐Juan, Yu, Lu, Gao, Shu‐Qin, Tan, Xiangshi, Lin, Ying‐Wu
Format: Article
Language:English
Subjects:
Catalytic Domain
covalent modification
Crystallography
Heme - chemistry
heme active site
Heme proteins
Hydrogen peroxide
Kinetics
Myoglobin - chemistry
Myoglobin - genetics
Myoglobin - metabolism
Myoglobins
Peroxidase
Phenols
Protein Conformation
protein engineering
Proteins
Sulfhydryl Compounds
Triazoles
X-ray structure
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Using myoglobin (Mb) as a model protein, we herein developed a facial approach to modifying the heme active site. A cavity was first generated in the heme distal site by F46 C mutation, and the thiol group of Cys46 was then used for covalently linked to exogenous ligands, 1H‐1,2,4‐triazole‐3‐thiol and 1‐(4‐hydroxyphenyl)‐1H‐pyrrole‐2,5‐dione. The engineered proteins, termed F46C‐triazole Mb and F46C‐phenol Mb, respectively, were characterized by X‐ray crystallography, spectroscopic and stopped‐flow kinetic studies. The results showed that both the heme coordination state and the protein function such as H2O2 activation and peroxidase activity could be efficiently regulated, which suggests that this approach might be generally applied to the design of functional heme proteins. Covalent modification: A facial approach was developed to regulate the heme active site of heme protein by cavity generation, followed by covalent modifications, as shown by the two case studies using myoglobin as a model protein.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.202300678