High resolution structure of Vibrio cholerae acylphosphatase (VcAcP) cage: Identification of drugs, location of its binding site and engineering to facilitate cage formation
| Autor: | Udayaditya Sen, S. N. Chatterjee, Seema Nath |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Models Molecular Stereochemistry Protein Conformation Protein subunit Biophysics Acylphosphatase medicine.disease_cause Crystallography X-Ray Protein Engineering Biochemistry 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Bacterial Proteins medicine Nucleotide Binding site Protein Structure Quaternary Molecular Biology Vibrio cholerae chemistry.chemical_classification Binding Sites Tryptophan Cell Biology Dynamic Light Scattering Acid Anhydride Hydrolases 030104 developmental biology chemistry Amino Acid Substitution 030220 oncology & carcinogenesis Chromatography Gel Mutagenesis Site-Directed Cage Cysteine |
| Zdroj: | Biochemical and biophysical research communications. 523(2) |
| ISSN: | 1090-2104 |
| Popis: | Protein cages have recently emerged as an extraordinary drug-delivery system due to its biocompatibility, biodegradability, low toxicity, ease to manipulate and engineer. We have reported earlier the formation and architecture of a do-decameric cage-like architecture of Vibrio cholerae acylphosphatase (VcAcP) at 3.1 A. High resolution (2.4 A) crystal structure of VcAcP cage, reported here, illuminates a potential binding site for sulphate/phosphate containing drugs whereas analysis of its subunit association and interfaces indicates high potential for cage engineering. Tryptophan quenching studies indeed discloses noteworthy binding with various sulphate/phosphate containing nucleotide-based drugs and vitamin B6 (PLP) demonstrating that exterior surface of VcAcP protein cage can be exploited as multifunctional carrier. Moreover, a quadruple mutant L30C/T68C/N40C/L81C-VcAcP (QM-VcAcP) capable to form an intricate disulphide bonded VcAcP cage has been designed. SEC, SDS-PAGE analysis and DLS experiment confirmed cysteine mediated engineered VcAcP cage formation. |
| Databáze: | OpenAIRE |
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