...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The FEBS journal >Structural and biochemical characterization of an atypical short-chain dehydrogenase/reductase reveals an unusual cofactor preference
【24h】

Structural and biochemical characterization of an atypical short-chain dehydrogenase/reductase reveals an unusual cofactor preference

机译：非典型短链脱氢酶/还原酶的结构和生化特征揭示了一个异常的辅因子偏爱

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Short-chain dehydrogenases/reductases (SDRs) encompass a large and functionally diverse family of enzymes with representative members in all kingdoms of life. Despite the wealth of reactions catalyzed by SDRs, they operate through a well-conserved andefficient reaction mechanism centered in a conserved catalytic tetrad (Asn-Scr-Tyr-Lys) and the employment of an appropriate cofactor. In recent years, SDRs that lack the signature catalytic tetrad have been identified, thus adding a perplexing twist toSDR functionality. In the present study, we report the crystal structure of SDRvv, an atypical SDR from Vibrio vulnificus devoid of the catalytic tetrad, thereby defining the structural signature of this apparent SDR family outlier. Further structural analysis of SDRvv in complex with its putative cofactor NADPFf, site-directed mutagenesis and binding studies via isothermal titration calo-rimctry, and further biochemical characterization have allowed us to dissect the cofactor preferences of SDRvv. Theretained capacity to bind the NADPFf cofactor, the conceivable existence of a proton relay and the conservation of the coordination distances between the key residues in the cofactor binding pocket define a first set of rules towards catalytic activityfor SDRvv. The findings of the present study set the stage for deriving the identity of the natural substrate of SDRvv and add a new twist to the structure-function landscape for Rossmann-fold-dcpcndcnt cofactor discrimination.
机译：短链脱氢酶/还原酶（SDR）涵盖了功能广泛的各种酶家族，在所有生命王国中均具有代表性。尽管SDR催化了丰富的反应，但它们仍通过以保守的催化四联体（Asn-Scr-Tyr-Lys）为中心的保守且有效的反应机制进行操作，并采用了适当的辅因子。近年来，已经鉴定出缺乏签名催化四联体的SDR，从而给SDR功能增加了困惑。在本研究中，我们报告了SDRvv的晶体结构，这是一种来自Vuliovulnificus的非典型SDR，缺乏催化四联体，从而定义了该表观SDR家族异常值的结构特征。 SDRvv与其推定的辅助因子NADPFf的复合物的进一步结构分析，定点诱变和通过等温滴定量热法的结合研究以及进一步的生化特征已使我们能够剖析SDRvv的辅助因子偏好。结合NADPFf辅因子的能力，可以想象的质子中继的存在以及辅因子结合口袋中关键残基之间配位距离的守恒定义了SDRvv催化活性的第一套规则。本研究的发现为推导SDRvv天然底物的身份奠定了基础，并为Rossmann-fold-dcpcndcnt辅助因子的识别增加了结构功能格局的新变化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号