Structural and biochemical insights into a hyperthermostable urate oxidase from Thermobispora bispora for hyperuricemia and gout therapy
| Autor: | Chun-Hua Hsu, Chen Yu Huang, Ting Syuan Hsu, Yi Chih Chiu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Gout Urate Oxidase Hyperuricemia Biochemistry Hydrophobic effect Thermobispora bispora Structural Biology Catalytic Domain Actinomycetales Enzyme Stability medicine Molecular Biology Thermostability chemistry.chemical_classification Thermophile Temperature Urate oxidase General Medicine Hydrogen-Ion Concentration medicine.disease Recombinant Proteins Kinetics Enzyme chemistry Structural Homology Protein |
| Zdroj: | International Journal of Biological Macromolecules. 188:914-923 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2021.08.081 |
| Popis: | Microbial urate oxidase has emerged as a potential source of therapeutic properties for hyperuricemia in arthritic gout and renal disease. The thermostability and long-term thermal tolerance of the enzyme need to be established to prolong its therapeutic effects. Here, we present the biochemical and structural aspects of a hyperthermostable urate oxidase (TbUox) from the thermophilic microorganism Thermobispora bispora. Enzymatic characterization of TbUox revealed that it was active over a wide range of temperatures, from 30 to 70 °C, with optimal activity at 65 °C and pH 8.0, which suggests its applicability under physiological conditions. Moreover, TbUox exhibits high thermostability from 10 to 65 °C, with Tm of 70.3 °C and near-neutral pH stability from pH 7.0 to 8.0 and high thermal tolerance. The crystal structures of TbUox revealed a distinct feature of the C-terminal loop extensions that may help with protein stability via inter-subunit interactions. In addition, the high thermal tolerance of TbUox may be contributed by the extensive inter-subunit contacts via salt bridges, hydrogen bonds, and hydrophobic interactions. The findings in this study provide a molecular basis for the thermophilic TbUox urate oxidase for application in hyperuricemia and gout therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect