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KMID : 0578320120330030229
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Molecules and Cells
2012 Volume.33 No. 3 p.229 ~ p.233
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High-Resolution Structure of Shikimate Dehydrogenase from Thermotoga maritima Reveals a Tightly Closed Conformation
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Lee Hyung-Ho
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Abstract
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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 shiki-mate dehydrogenases. The crystal structure of SDH from T. maritima was determined at 1.45 A by molecular replace-ment. SDH from T. maritima showed a monomeric archi-tecture. The overall structure of SDH from T. maritima comprises the N-terminal ?/? sandwich domain for sub-strate binding and the C-terminal domain for NADP bind-ing. 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, ?7 moves toward the active site (~5 A), 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 bind-ing site of SDHs, is expected to supplement the existing structural data and will be useful for structure-based anti-bacterial discovery against SDHs.
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KEYWORD
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aroE, shikimate dehydrogenase, shikimate pathway, Thermotoga maritima
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