Department of Bio and Nano Chemistry, Kookmin University, Seoul 136-702, Korea.
Mol Cells. 2012 Mar;33(3):229-33. doi: 10.1007/s10059-012-2200-x. Epub 2011 Nov 15.
Shikimate dehydrogenase (SDH), which catalyses the NADPH-dependent reduction of 3-dehydroshikimate to shikimate in the shikimate pathway, is an attractive target for the development of herbicides and antimicrobial agents. Structural analysis of a SDH from Thermotoga maritima encoded by the Tm0346 gene was performed to facilitate further structural comparisons between the various shikimate dehydrogenases. The crystal structure of SDH from T. maritima was determined at 1.45 SDH from T. maritima showed a monomeric architecture. The overall structure of SDH from T. maritima comprises the N-terminal α/β sandwich domain for substrate binding and the C-terminal domain for NADP binding. When the T. maritima SDH structure was compared with those of the SDHs from other species, the SDH from T. maritima was in a tightly closed conformation, which should be open for catalysis. Notably, α7 moves toward the active site (∼5 Å), which forces the SDH of T. maritima in a more closed form. Four ammonium sulfate (AMS) ions were identified in the structure. They were located in the active site and appeared to mimic the role of the substrate in terms of the enzyme activity and stability. The new high resolution structural information reported in this study, including the AMS binding sites as a potent inhibitor binding site of SDHs, is expected to supplement the existing structural data and will be useful for structure-based antibacterial discovery against SDHs.
莽草酸脱氢酶（SDH）在莽草酸途径中催化 NADPH 依赖性的 3-脱氢莽草酸还原为莽草酸，是开发除草剂和抗菌剂的有吸引力的靶标。为了促进各种莽草酸脱氢酶之间的进一步结构比较，对编码自 Thermotoga maritima 的 Tm0346 基因的 SDH 进行了结构分析。测定了来自 T. maritima 的 SDH 的晶体结构，分辨率为 1.45 Å。来自 T. maritima 的 SDH 显示出单体结构。T. maritima 的 SDH 的整体结构包括用于底物结合的 N 端α/β 夹心结构域和用于 NADP 结合的 C 端结构域。当将 T. maritima SDH 结构与来自其他物种的 SDH 结构进行比较时，T. maritima 的 SDH 处于紧密关闭构象，这应该是用于催化的开放构象。值得注意的是，α7 向活性位点移动（约 5 Å），这迫使 T. maritima 的 SDH 处于更封闭的形式。在结构中鉴定了四个硫酸铵（AMS）离子。它们位于活性位点，并且在酶活性和稳定性方面似乎模拟了底物的作用。本研究报告的新的高分辨率结构信息，包括 AMS 结合位点作为 SDH 的有效抑制剂结合位点，预计将补充现有的结构数据，并将有助于基于结构的抗菌药物发现针对 SDH。
