Elucidation of pH-Induced Protein Structural Changes: A Combined 2D IR and Computational Approach.
Biochemistry
; 62(2): 451-461, 2023 01 17.
Article
em En
| MEDLINE
| ID: mdl-36573496
ABSTRACT
The acid-base behavior of amino acids plays critical roles in several biochemical processes. Depending on the interactions with the protein environment, the pKa values of these amino acids shift from their respective solution values. As the side chains interact with the polypeptide backbone, a pH-induced change in the protonation state of aspartic and glutamic acids might significantly influence the structure and stability of a protein. In this work, we have combined two-dimensional infrared spectroscopy and molecular dynamics simulations to elucidate the pH-induced structural changes in an antimicrobial enzyme, lysozyme, over a wide range of pH. Simultaneous measurements of the carbonyl signals arising from the backbone and the acidic side chains provide detailed information about the pH dependence of the local and global structural features. An excellent agreement between the experimental and the computational results allowed us to obtain a residue-specific molecular understanding. Although lysozyme retains the helical structure for the entire pH range, one distinct loop region (residues 65-75) undergoes local structural deformation at low pH. Interestingly, combining our experiments and simulations, we have identified the aspartic acid residues in lysozyme, which are influenced the most/least by pH modulation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Muramidase
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Índia