A molecular dynamics approach on the Y393C variant of protein disulfide isomerase A1
| Autor: | Rosa E. Mares-Alejandre, Marco A. Ramos-Ibarra, Pablo A. Madero‐Ayala |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Chemical biology
Procollagen-Proline Dioxygenase Protein Disulfide-Isomerases Single-nucleotide polymorphism Molecular Dynamics Simulation Endoplasmic Reticulum 01 natural sciences Biochemistry Craniosynostoses Oxidoreductase Drug Discovery Humans Eye Abnormalities Protein disulfide-isomerase Gene Pharmacology chemistry.chemical_classification biology 010405 organic chemistry Chemistry Oxidative folding Endoplasmic reticulum Organic Chemistry Osteogenesis Imperfecta 0104 chemical sciences 010404 medicinal & biomolecular chemistry Chaperone (protein) biology.protein Molecular Medicine Oxidation-Reduction Hydrocephalus |
| Zdroj: | Chemical biologydrug designREFERENCES. 96(6) |
| ISSN: | 1747-0285 |
| Popis: | Human protein disulfide isomerase A1 (PDIA1) shows both catalytic (i.e., oxidoreductase) and non-catalytic (i.e., chaperone) activities and plays a crucial role in the oxidative folding of proteins within the endoplasmic reticulum. PDIA1 dysregulation is a common trait in numerous pathophysiological conditions, including neurodegenerative disorders and cancerous diseases. The 1178A>G mutation of the human PDIA1-encoding gene is a non-synonymous single nucleotide polymorphism detected in patients with Cole-Carpenter syndrome type 1 (CSS1), a particularly rare bone disease. In vitro studies showed that the encoded variant (PDIA1 Y393C) exhibits limited oxidoreductase activity. To gain knowledge on the structure-function relationship, we undertook a molecular dynamics (MD) approach to examine the structural stability of PDIA1 Y393C. Results showed that significant conformational changes are the structural consequence of the amino acid substitution Tyr>Cys at position 393 of the PDIA1 protein. This structure-based study provides further knowledge about the molecular origin of CCS1. |
| Databáze: | OpenAIRE |
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