Twists in catalysis:: Alternating conformations of Escherichia coli thioredoxin reductase
Twists in catalysis:: Alternating conformations of Escherichia coli thioredoxin reductase
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DOI：
10.1126/science.289.5482.1190
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发表时间：
2000-08-18
期刊：
影响因子：
56.9
通讯作者：
Ludwig, ML
中科院分区：
文献类型：
--
作者：
Lennon, BW;Williams, CH;Ludwig, ML
在来自大肠杆菌的硫氧还蛋白还原酶（TrxR）中，黄素腺嘌呤二核苷酸（FAD）辅因子的还原和再氧化循环取决于FAD和NADPH（还原形式的烟酰胺腺嘌呤二核苷酸磷酸）结构域的限速重排。我们描述了E. coliTrxR，分辨率为3.0埃。这两个结构域的取向允许NADPH还原FAD和蛋白质底物硫氧还蛋白氧化酶二硫醇。Kuriyan及其同事描述的替代构象允许还原当量从还原FAD内部转移到活性位点二硫化物。这些结构的比较表明，两种构象之间的切换涉及一个“球窝”的运动，其中吡啶核苷酸结合域旋转67度。
In thioredoxin reductase (TrxR) from Escherichia coli, cycles of reduction and reoxidation of the flavin adenine dinucleotide (FAD) cofactor depend on rate-limiting rearrangements of the FAD and NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) domains. We describe the structure of the ftavin-reducing conformation of E. coli TrxR at a resolution of 3.0 angstroms. The orientation of the two domains permits reduction of FAD by NADPH and oxidation of the enzyme dithiol by the protein substrate, thioredoxin. The alternate conformation, described by Kuriyan and co-workers, permits internal transfer of reducing equivalents from reduced FAD to the active-site disulfide. Comparison of these structures demonstrates that switching between the two conformations involves a "ball-and-socket" motion in which the pyridine nucleotide-binding domain rotates by 67 degrees.