Structural stability of the SARS-CoV-2 main protease: Can metal ions affect function?
| Autor: | Roberto A. Garza-López, John J. Kozak, Harry B. Gray |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cytochrome
Stereochemistry medicine.medical_treatment 010402 general chemistry 01 natural sciences Biochemistry Article Metal Inorganic Chemistry chemistry.chemical_compound medicine Histidine Protease Inhibitors Globin Cysteine Coronavirus 3C Proteases Protein Unfolding chemistry.chemical_classification Protease biology 010405 organic chemistry Protein Stability SARS-CoV-2 Cytoglobin Cobalt 0104 chemical sciences Enzyme chemistry Myoglobin visual_art biology.protein visual_art.visual_art_medium Protein Binding |
| Zdroj: | Journal of Inorganic Biochemistry |
| Popis: | We have investigated the structural stability of the SARS-CoV-2 main protease monomer (Mpro). We quantified the spatial and angular changes in the structure using two independent analyses, one based on a spatial metrics (δ, ratio), the second on angular metrics. The order of unfolding of the 10 helices in Mpro is characterized by beta vs alpha plots similar to those of cytochromes and globins. The longest turning region is anomalous in the earliest stage of unfolding. In an investigation of excluded-volume effects, we found that the maximum spread in average molecular-volume values for Mpro, cytochrome c-b562, cytochrome c’, myoglobin, and cytoglobin is ~10 Å3. This apparent universality is a consequence dominant contributions from six residues: ALA, ASP, GLU, LEU, LYS and VAL. Of the seven Mpro histidines, residues 41, 163, 164, and 246 are in stable H-bonded regions; metal ion binding to one or more of these residues could break up the H-bond network, thereby affecting protease function. Our analysis also indicated that metal binding to cysteine residues 44 and 145 could disable the enzyme. Graphical abstract The main protease is a homodimer that cuts polyproteins into functional pieces for the production of new virons. Can metal ions inhibit this enzyme?Unlabelled Image Highlights • Excluded volume in the folded SARS-CoV-2 main protease is estimated. • Helix stabilities in the SARS-CoV-2 main protease differ dramatically. • Metal ion binding could inhibit the SARS-CoV-2 main protease. |
| Databáze: | OpenAIRE |
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