对肌醇焦磷酸周转的结构洞察。
Structural insight into inositol pyrophosphate turnover.
作者信息
Shears Stephen B, Weaver Jeremy D, Wang Huanchen
机构信息
Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, PO Box 12233, NC 27709, USA.
出版信息
Adv Biol Regul. 2013 Jan;53(1):19-27. doi: 10.1016/j.jbior.2012.10.002. Epub 2012 Oct 11.
The diphosphoinositol polyphosphates ("inositol pyrophosphates"; PP-InsPs) regulate many cellular processes in eukaryotes, including stress responses, apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, telomere maintenance, insulin signaling and neutrophil activation. Thus, the enzymes that control the metabolism of the PP-InsPs serve important cell signaling roles. In order to fully characterize how these enzymes are regulated, we need to determine the atomic-level architecture of their active sites. Only then can we fully appreciate reaction mechanisms and their modes of regulation. In this review, we summarize published information obtained from the structural analysis of a human diphosphoinositol polyphosphate phosphohydrolase (DIPP), and a human diphosphoinositol polyphosphate kinase (PPIP5K). This work includes the analysis of crystal complexes with substrates, products, transition state analogs, and a novel phosphonoacetate substrate analog.
二磷酸肌醇多磷酸（“肌醇焦磷酸”；PP-InsPs）调节真核生物中的许多细胞过程，包括应激反应、细胞凋亡、囊泡运输、细胞骨架动力学、胞吐作用、端粒维持、胰岛素信号传导和中性粒细胞活化。因此，控制PP-InsPs代谢的酶发挥着重要的细胞信号传导作用。为了全面表征这些酶是如何被调节的，我们需要确定其活性位点的原子水平结构。只有这样，我们才能充分理解反应机制及其调节模式。在这篇综述中，我们总结了从人类二磷酸肌醇多磷酸磷酸水解酶（DIPP）和人类二磷酸肌醇多磷酸激酶（PPIP5K）的结构分析中获得的已发表信息。这项工作包括对与底物、产物、过渡态类似物和一种新型膦酰乙酸底物类似物的晶体复合物的分析。
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