Department of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan.
J Am Chem Soc. 2010 Dec 8;132(48):17080-3. doi: 10.1021/ja1077574. Epub 2010 Nov 15.
Two contradictory models have been proposed for the binding mode of the substrate xanthine to and its activation mechanism by xanthine oxidoreductase. In an effort to distinguish between the two models, we determined the crystal structures of the urate complexes of the demolybdo-form of the D428A mutant of rat xanthine oxidoreductase at 1.7 Å and of the reduced bovine milk enzyme at 2.1 Å, the latter representing a reaction intermediate. The results clearly indicate the catalytically relevant binding mode of the substrate xanthine.
两种相互矛盾的模型被提出来解释黄嘌呤底物与黄嘌呤氧化还原酶的结合模式及其激活机制。为了区分这两种模型，我们测定了 D428A 突变的去钼大鼠黄嘌呤氧化还原酶尿酸复合物的晶体结构（分辨率为 1.7Å）和还原态牛乳酶的晶体结构（分辨率为 2.1Å），后者代表反应中间态。结果清楚地表明了底物黄嘌呤的催化相关结合模式。
