蛋白质药物尿酸氧化酶 - 抑制剂复合物的晶体结构，分辨率为2.05埃。
Crystal structure of the protein drug urate oxidase-inhibitor complex at 2.05 A resolution.
作者信息
Colloc'h N, el Hajji M, Bachet B, L'Hermite G, Schiltz M, Prangé T, Castro B, Mornon J P
机构信息
Systèmes Moléculaires et Biologie Structurale, CNRS URA09, Université Paris VI et Paris VII, France.
出版信息
Nat Struct Biol. 1997 Nov;4(11):947-52. doi: 10.1038/nsb1197-947.
The gene coding for urate oxidase, an enzyme that catalyzes the oxidation of uric acid to allantoin, is inactivated in humans. Consequently, urate oxidase is used as a protein drug to overcome severe disorders induced by uric acid accumulation. The structure of the active homotetrameric enzyme reveals the existence of a small architectural domain that we call T-fold (for tunnelling-fold) domain. It assembles to form a perfect unusual dimeric alpha 8 beta 16 barrel. Urate oxidase may be the archetype of an expanding new family of tunnel-shaped proteins that now has three members; tetrahydropterin synthase, GTP cyclohydrolase I and urate oxidase. The structure of the active site of urate oxidase around the 8-azaxanthine inhibitor reveals an original mechanism of oxidation that does not require any ions or prosthetic groups.
编码尿酸氧化酶（一种催化尿酸氧化为尿囊素的酶）的基因在人类中失活。因此，尿酸氧化酶被用作一种蛋白质药物，以克服由尿酸积累引起的严重疾病。活性同四聚体酶的结构揭示了一个我们称为T折叠（隧道折叠）结构域的小建筑结构域的存在。它组装形成一个完美的异常二聚体α8β16桶状结构。尿酸氧化酶可能是一个不断扩大的新的隧道状蛋白质家族的原型，该家族目前有三个成员：四氢生物蝶呤合酶、GTP环化水解酶I和尿酸氧化酶。围绕8-氮杂黄嘌呤抑制剂的尿酸氧化酶活性位点的结构揭示了一种不需要任何离子或辅基的原始氧化机制。
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