Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite
详细信息 查看全文
- 作者：Jennifer J. Thiaville ; Jake Flood ; Svetlana Yurgel ; Laurence Prunetti ; Mona Elbadawi-Sidhu ; Geoffrey Hutinet ; Farhad Forouhar ; Xinshuai Zhang ; Venkateswaran Ganesan ; Patrick Reddy ; Oliver Fiehn ; J. A. Gerlt ; John F. Hunt ; Shelley D. Copley ; Valérie de Crécy-Lagard
- 刊名：ACS Chemical Biology
- 出版年：2016
- 出版时间：August 19, 2016
- 年：2016
- 卷：11
- 期：8
- 页码：2304-2311
- 全文大小：507K
- 年卷期：0
- ISSN：1554-8937
文摘
DUF1537 is a novel family of kinases identified by comparative genomic approaches. The family is widespread and found in all sequenced plant genomes and 16% of sequenced bacterial genomes. DUF1537 is not a monofunctional family and contains subgroups that can be separated by phylogenetic and genome neighborhood context analyses. A subset of the DUF1537 proteins is strongly associated by physical clustering and gene fusion with the PdxA2 family, demonstrated here to be a functional paralog of the 4-phosphohydroxy-l-threonine dehydrogenase enzyme (PdxA), a central enzyme in the synthesis of pyridoxal-5′-phosphate (PLP) in proteobacteria. Some members of this DUF1537 subgroup phosphorylate l-4-hydroxythreonine (4HT) into 4-phosphohydroxy-l-threonine (4PHT), the substrate of PdxA, in vitro and in vivo. This provides an alternative route to PLP from the toxic antimetabolite 4HT that can be directly generated from the toxic intermediate glycolaldehyde. Although the kinetic and physical clustering data indicate that these functions in PLP synthesis are not the main roles of the DUF1537-PdxA2 enzymes, genetic and physiological data suggest these side activities function has been maintained in diverse sets of organisms.