来自……的1-脱氧-D-木酮糖-5-磷酸合酶的机制研究 。 （原文中“from”后面缺少具体内容）
Mechanistic Studies of 1-Deoxy-D-Xylulose-5-Phosphate Synthase from .
作者信息
Handa Sumit, Dempsey Daniel R, Ramamoorthy Divya, Cook Nanci, Guida Wayne C, Spradling Tyler J, White Justin K, Woodcock H Lee, Merkler David J
机构信息
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Departments of Medicine, Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Brigham and Women's Hospital, Boston, UK.
出版信息
Biochem Mol Biol J. 2018;4(1). doi: 10.21767/2471-8084.100051. Epub 2018 Jan 29.
The non-mevalonate dependent (NMVA) pathway for the biosynthesis of isopentenyl pyrophosphate and dimethylallyl pyrophosphate is the sole source of these terpenoids for the production of isoprenoids in the apicomplexan parasites, in many eubacteria, and in plants. The absence of this pathway in higher organisms has opened a new platform for the development of novel antibiotics and anti-malarials. The enzyme catalyzing the first step of the NMVA pathway is 1-deoxy-D-xylulose-5-phosphate synthase (DXPS). DXPS catalyzes the thiamine pyrophosphate- and Mg (II)-dependent conjugation of pyruvate and D-glyceraldehyde-3-phosphate to form 1-deoxy-D-xylulose-5-phosphate and CO. The kinetic mechanism of DXPS from most consistent with our data is random sequential as shown using a combination of kinetic analysis and product and dead-end inhibition studies. The role of active site amino acids, identified by sequence alignment to other DXPS proteins, was probed by constructing and analyzing the catalytic efficacy of a set of targeted site-directed mutants.
异戊烯基焦磷酸和二甲基烯丙基焦磷酸生物合成的非甲羟戊酸途径（NMVA途径）是顶复门寄生虫、许多真细菌和植物中用于生产类异戊二烯的这些萜类化合物的唯一来源。高等生物中缺乏该途径为新型抗生素和抗疟疾药物的开发开辟了一个新平台。催化NMVA途径第一步的酶是1-脱氧-D-木酮糖-5-磷酸合酶（DXPS）。DXPS催化硫胺素焦磷酸和Mg（II）依赖的丙酮酸与D-甘油醛-3-磷酸的共轭反应，形成1-脱氧-D-木酮糖-5-磷酸和CO。使用动力学分析以及产物和终产物抑制研究相结合的方法表明，与我们的数据最一致的DXPS动力学机制是随机顺序机制。通过构建和分析一组靶向定点突变体的催化效率，探究了通过与其他DXPS蛋白进行序列比对鉴定出的活性位点氨基酸的作用。
Zotero 插件