The high-resolution structure of dihydrodipicolinate synthase from Escherichia coli bound to its first substrate, pyruvate
The high-resolution structure of dihydrodipicolinate synthase from Escherichia coli bound to its first substrate, pyruvate
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DOI：
10.1107/s1744309108033654
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发表时间：
2008-12-01
影响因子：
0.9
通讯作者：
Dobson, Renwick C. J.
中科院分区：
文献类型：
--
作者：
Devenish, Sean R. A.;Gerrard, Juliet A.;Dobson, Renwick C. J.
二氢吡啶二羧酸合酶（DHDPS）介导生物合成（S）-赖氨酸和内消旋-二氨基庚二酸的关键第一反应，这些分子在细菌细胞壁中起关键的交联作用。DHDPS的有效抑制剂将代表一种有用的抗菌剂;尽管付出了巨大的努力，但尚未找到合适的抑制剂。为了检查DHDPS活性位点的特异性，将该酶与底物类似物草酰乙酸共结晶。得到的晶体衍射到2.0埃分辨率，但蛋白质结构的溶液显示丙酮酸盐结合在活性位点而不是草酰乙酸。动力学分析证实，草酰乙酸的脱羧反应不是由DHDPS催化的，而是一个缓慢的自发化学过程。
Dihydrodipicolinate synthase (DHDPS) mediates the key first reaction common to the biosynthesis of (S)-lysine and meso-diaminopimelate, molecules which play a crucial cross-linking role in bacterial cell walls. An effective inhibitor of DHDPS would represent a useful antibacterial agent; despite extensive effort, a suitable inhibitor has yet to be found. In an attempt to examine the specificity of the active site of DHDPS, the enzyme was cocrystallized with the substrate analogue oxaloacetate. The resulting crystals diffracted to 2.0 angstrom resolution, but solution of the protein structure revealed that pyruvate was bound in the active site rather than oxaloacetic acid. Kinetic analysis confirmed that the decarboxylation of oxaloacetate was not catalysed by DHDPS and was instead a slow spontaneous chemical process.