Variation on a theme of SDR:: dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmID) shows a new Mg2+-dependent dimerization mode
Variation on a theme of SDR:: dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmID) shows a new Mg2+-dependent dimerization mode
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DOI：
10.1016/s0969-2126(02)00770-0
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发表时间：
2002-06-01
期刊：
影响因子：
5.7
通讯作者：
Naismith, JH
中科院分区：
文献类型：
--
作者：
Blankenfeldt, W;Kerr, ID;Naismith, JH
在NAD(P)H-和Mg2+依赖性反应中，dtdp -6-脱氧-l -lyxo-4-己糖还原酶（RmID）催化dtdp -d -葡萄糖转化为dtdp -l -鼠李糖的最后一步。l -鼠李糖是一种生物合成的抗菌靶点。从肠炎沙门氏菌血清鼠伤寒沙门氏菌中分离得到的RmID的结构已被确定，并与NADH、NADPH和dtdp - l -鼠李糖形成络合物。RmID与其他短链脱氢酶的不同之处在于它具有一种含有Mg2+的新型二聚体界面。酶催化包括氢化物从辅助因子的烟酰胺环转移到底物的C4'-羰基。底物通过一个保守的酪氨酸的质子化作用被激活。NAD(P)H结合在溶剂暴露的裂缝中，允许容易的替换。我们提出了SDR酶催化三联体中保守的丝氨酸/苏氨酸残基的新作用。
dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmID) catalyzes the final step in the conversion of dTDP-D-glucose to dTDP-L-rhamnose in an NAD(P)H- and Mg2+-dependent reaction. L-rhamnose biosynthesis is an antibacterial target. The structure of RmID from Salmonella enterica serovar Typhimurium has been determined, and complexes with NADH, NADPH, and dTDP-L-rhamnose are reported. RmID differs from other short chain dehydrogenases in that it has a novel dimer interface that contains Mg2+. Enzyme catalysis involves hydride transfer from the nicotinamide ring of the cofactor to the C4'-carbonyl group of the substrate. The substrate is activated through protonation by a conserved tyrosine. NAD(P)H is bound in a solvent-exposed cleft, allowing facile replacement. We suggest a novel role for the conserved serine/threonine residue of the catalytic triad of SDR enzymes.