Li Kunhua, Li Gengnan, Bradbury Louis M T, Hanson Andrew D, Bruner Steven D
Department of Chemistry, University of Florida, Gainesville, FL 32611, U.S.A.
Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, U.S.A.
Biochem J. 2016 Feb 1;473(3):277-84. doi: 10.1042/BJ20150980. Epub 2015 Nov 12.
Homocysteine S-methyltransferases (HMTs, EC 2.1.1.0) catalyse the conversion of homocysteine to methionine using S-methylmethionine or S-adenosylmethionine as the methyl donor. HMTs play an important role in methionine biosynthesis and are widely distributed among micro-organisms, plants and animals. Additionally, HMTs play a role in metabolite repair of S-adenosylmethionine by removing an inactive diastereomer from the pool. The mmuM gene product from Escherichia coli is an archetypal HMT family protein and contains a predicted zinc-binding motif in the enzyme active site. In the present study, we demonstrate X-ray structures for MmuM in oxidized, apo and metallated forms, representing the first such structures for any member of the HMT family. The structures reveal a metal/substrate-binding pocket distinct from those in related enzymes. The presented structure analysis and modelling of co-substrate interactions provide valuable insight into the function of MmuM in both methionine biosynthesis and cofactor repair.
同型半胱氨酸S-甲基转移酶（HMTs，EC 2.1.1.0）以S-甲基蛋氨酸或S-腺苷甲硫氨酸作为甲基供体，催化同型半胱氨酸转化为蛋氨酸。HMTs在蛋氨酸生物合成中起重要作用，广泛分布于微生物、植物和动物中。此外，HMTs通过从池中去除无活性的非对映异构体，在S-腺苷甲硫氨酸的代谢物修复中发挥作用。来自大肠杆菌的mmuM基因产物是一种典型的HMT家族蛋白，在酶活性位点含有一个预测的锌结合基序。在本研究中，我们展示了氧化型、脱辅基型和金属化型MmuM的X射线结构，这是HMT家族任何成员的首个此类结构。这些结构揭示了一个与相关酶不同的金属/底物结合口袋。所呈现的结构分析和共底物相互作用建模为MmuM在蛋氨酸生物合成和辅因子修复中的功能提供了有价值的见解。
