Chiu Y.-CHsu T.-SHuang C.-YCHUN-HUA HSU2022-04-252022-04-25202101418130https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113685815&doi=10.1016%2fj.ijbiomac.2021.08.081&partnerID=40&md5=b3bdc69ddba9c9a2e76de789616fbb03https://scholars.lib.ntu.edu.tw/handle/123456789/606023Microbial 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. ? 2021Crystal structureHyperthermostableUricaserecombinant proteinurate oxidaseActinomycetaleschemistryenzyme active siteenzyme stabilityenzymologygouthyperuricemiakineticsmetabolismmolecular modelpHstructural homologytemperatureCatalytic DomainEnzyme StabilityGoutHydrogen-Ion ConcentrationHyperuricemiaKineticsModels, MolecularRecombinant ProteinsStructural Homology, ProteinTemperatureUrate Oxidase[SDGs]SDG3[SDGs]SDG6journal article10.1016/j.ijbiomac.2021.08.081344036752-s2.0-85113685815