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首页> 外文期刊>The FEBS journal >Thiamin diphosphate in biological chemistry: analogues of thiamin diphosphate in studies of enzymes and riboswitches
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Thiamin diphosphate in biological chemistry: analogues of thiamin diphosphate in studies of enzymes and riboswitches

机译：生物化学中的硫胺素二磷酸盐：酶和核糖开关研究中的硫胺素二磷酸盐类似物

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摘要

The role of thiamin diphosphate (ThDP) as a cofactor for enzymes has been known for many decades. This minireview covers the progress made in understanding the catalytic mechanism of ThDP-dependent enzymes through the use of ThDP analogues. Many such analogues have been synthesized and have provided information on the functional groups necessary for the binding and catalytic activity of the cofactor. Through these studies, the important role of hydrophobic interactions in stabilizing reaction intermediates in the catalytic cycle has been recognized. Stable analogues of intermediates in the ThDP-catalysed reaction mechanism have also been synthesized and crystallographic studies using these analogues have allowed enzyme structures to be solved that represent snapshots of the reaction in progress. As well as providing mechanistic information about ThDP-dependent enzymes, many analogues are potent inhibitors of these enzymes. The potential of these compounds as therapeutic targets and as important herbicidal agents is discussed. More recently, the way that ThDP regulates the genes for its own biosynthesis through the action of riboswitches has been discovered. This opens a new branch of thiamin research with the potential to provide new therapeutic targets in the fight against infection.
机译：硫胺素二磷酸酯（ThDP）作为酶的辅助因子的作用已有数十年了。这篇小型综述涵盖了通过使用ThDP类似物来理解ThDP依赖型酶的催化机制所取得的进展。已经合成了许多这样的类似物，并提供了有关辅因子的结合和催化活性所必需的官能团的信息。通过这些研究，已经认识到疏水相互作用在稳定催化循环中的反应中间体方面的重要作用。还已经合成了ThDP催化的反应机理中中间体的稳定类似物，并且使用这些类似物进行的晶体学研究已经解决了代表反应进行中的快照的酶结构。除了提供有关ThDP依赖性酶的机制信息外，许多类似物也是这些酶的有效抑制剂。讨论了这些化合物作为治疗靶标和重要除草剂的潜力。最近，已经发现了ThDP通过核糖开关的作用调节基因以进行自身生物合成的方式。这为硫胺素研究开辟了一个新的分支，有望为抗击感染提供新的治疗靶标。

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