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首页> 外文期刊>Biochemistry >Epimerization at carbon-5 ' of (5 ' R)-[5 ',H-2]adenosylcobalamin by ribonucleoside triphosphate reductase: Cysteine 408-independent cleavage of the Co-C5 ' bond
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Epimerization at carbon-5 ' of (5 ' R)-[5 ',H-2]adenosylcobalamin by ribonucleoside triphosphate reductase: Cysteine 408-independent cleavage of the Co-C5 ' bond

机译：碳-5'（5'R） - [5'，H-2]亚苯基钴氨基核苷三磷酸还原酶的亚苯甲酰胺：Cysteine 408依赖于CO-C5'键

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The adenosylcobalamin-dependent ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii catalyzes the reduction of ribonucleoside triphosphates to deoxyribonucleoside triphosphates. RTPR also catalyzes the exchange of the C5'-hydrogens of adenosylcobalalamin with solvent hydrogen. A thiyl radical located on Cys 408 is generated by reaction of adenosylcobalamin at the active site and is proposed to be the intermediate for both the nucleotide reduction and the 5'-hydrogen exchange reactions. In the present research, a stereochemical approach is used to study the mechanism of the Co-C5' bond cleavage of adenosylcobalamin in the reaction of RTPR. When stereoselectively deuterated coenzyme, (5'R)-[5'-H-2(1)] adenosylcobalamin (5'R/S = 3:1), was incubated with RTPR or the Cys 408 viariants, C408A-RTPR and C408S-RTPR in the presence of dGTP, the deuterium at the 5'-carbon was stereochemically scrambled, leading to epimerization of the (5'S)-[5'-H-2(1)]- and (5R)-[5'-H-2(1)]-isotopomers. Observation of epimerization with mutated RTPR proves that transient cleavage of the Co-C5' bond occurs in the absence of the thiol group on Cys 408. The rate constants for epimerization by RTPR, C408A-RTPR, and C408S-RTPRs in the presence of dGTP are 5.1, 0.28, and 0.42 s(-1), respectively. Only the wild-type RTPR catalyzes the 5'-hydrogen exchange reaction. Both epimerization and 5'-hydrogen exchange reactions are stimulated by the allosteric effector dGTP, and epimerization is not detected in the absence of the effector. Mechanistic implications with respect to wt-RTPR-mediated carbon cobalt bond homolysis and the intermediacy of the 5'-deoxyadenosyl radical will be presented. [References: 24]
机译：来自乳酸杆菌的腺苷依赖性核糖核糖核苷三磷酸还原酶（RTPR）催化核糖核苷三磷酸核糖核苷三磷酸三磷酸三磷酸三磷酸。 RTPR还催化与溶剂氢的腺苷钴胺的C5'-氢的交换。位于Cys 408上的硫代基团通过腺苷钴胺素在活性位点的反应产生，并且被提出为核苷酸还原和5'-氢交换反应的中间体。在本研究中，使用立体化学方法来研究腺瘤钴胺蛋白在RTPR反应中的CO-C5'键切割的机理。当立体选择性氘代酶（5'R） - [5'-H-2（1）]腺苷（5'R / s = 3：1），与RTPR或Cys 408 viariants，C408A-RTPR和C408孵育-RTPR在存在DGTP的情况下，5'-碳的氘是立体化学炒的，导致（5'） - [5'-H-2（1）] - 和（5R） - [5' - [5' H-2（1）] - 同位素。用突变的RTPR观察结果证明了CO-C5'键的瞬时切割发生在Cys 408上的硫醇基团的情况下。在DGTP存在下，RTPR，C408A-RTPR和C408S-RTPRS的速率常数分别为5.1,0.28和0.42秒（-1）。只有野生型RTPR催化5'-氢交换反应。通过仿生效应DGTP刺激差异和5'-氢交换反应，在没有效应器的情况下未检测到映射。将介绍关于WT-RTPR介导的碳钴键均解和5'-脱氧糖基的中介症的机械效力。 [参考：24]

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