https://scholars.lib.ntu.edu.tw/handle/123456789/606023
標題: | Structural and biochemical insights into a hyperthermostable urate oxidase from Thermobispora bispora for hyperuricemia and gout therapy | 作者: | Chiu Y.-C Hsu T.-S Huang C.-Y CHUN-HUA HSU |
關鍵字: | Crystal structure;Hyperthermostable;Uricase;recombinant protein;urate oxidase;Actinomycetales;chemistry;enzyme active site;enzyme stability;enzymology;gout;hyperuricemia;kinetics;metabolism;molecular model;pH;structural homology;temperature;Catalytic Domain;Enzyme Stability;Gout;Hydrogen-Ion Concentration;Hyperuricemia;Kinetics;Models, Molecular;Recombinant Proteins;Structural Homology, Protein;Temperature;Urate Oxidase | 公開日期: | 2021 | 卷: | 188 | 起(迄)頁: | 914-923 | 來源出版物: | International Journal of Biological Macromolecules | 摘要: | 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. ? 2021 |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113685815&doi=10.1016%2fj.ijbiomac.2021.08.081&partnerID=40&md5=b3bdc69ddba9c9a2e76de789616fbb03 https://scholars.lib.ntu.edu.tw/handle/123456789/606023 |
ISSN: | 01418130 | DOI: | 10.1016/j.ijbiomac.2021.08.081 |
顯示於: | 農業化學系 |
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