S-Adenosylmethionine conformations in solution and in protein complexes:: Conformational influences of the sulfonium group
S-Adenosylmethionine conformations in solution and in protein complexes:: Conformational influences of the sulfonium group
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DOI：
10.1021/bi025682c
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发表时间：
2002-06-18
期刊：
影响因子：
2.9
通讯作者：
Bock, CW
中科院分区：
文献类型：
--
作者：
Markham, GD;Norrby, PO;Bock, CW
S-腺苷甲硫氨酸（S-Adenosylmethionine，S-Met）和其他锍离子在所有生物体的代谢中起着重要作用。已通过NMR和计算研究的构象偏好的THEMOMet和其他两个生物学上重要的锍离子，S-甲基蛋氨酸和二甲基磺基丙酸，进行了研究。锍中心的分子力学参数已开发的琥珀色力场，允许分析NMR结果，并使不同的构象的相对能量的比较，已发现在晶体结构的复合物与蛋白质。S-甲基甲硫氨酸和S-二甲基磺基丙酸盐在水溶液中采用各种构象;与真空计算中发现的优选构象相比，锍硫和羧酸酯基团之间具有静电相互作用的构象并不明显有利。核Overhauser效应的测量和计算结果表明，主要是反构象的糖苷键与各种构象的甲硫氨酰C-α-C-β和C-β-C-γ键。带正电荷的锍硫靠近核糖环中带负电的氧的硫代蛋氨酸构象是常见的。比较NMR的结果，为NH4Met与那些不带电荷的S-腺苷高半胱氨酸和5'-甲硫基腺苷，和阴离子ATP，表明溶液的构象主要不是由分子电荷。在20个已报道的蛋氨酸-蛋白质复合物的结构中，发现了反式和顺式糖苷扭转角，甲硫氨酰基在与从锍中心转移甲基的酶的复合物中通常采用延伸构象，但在与不催化涉及硫的反应并且可以仅使用锍硫作为结合位点的蛋白质的复合物中更多地折叠。在这些晶体结构中的构象能量的DMET是可比的DMET在溶液中发现的。锍硫与四种蛋白质结构中的蛋白质杂原子处于货车范德华接触，这反映了能量上有利的接触。很少观察到锍与芳环的相互作用。
S-Adenosylmethionine (AdoMet) and other sulfonium ions play central roles in the metabolism of all organisms. The conformational preferences of AdoMet and two other biologically important sulfonium ions, S-methylmethionine and dimethylsulfonioproprionic acid, have been investigated by NMR and computational studies. Molecular mechanics parameters for the sulfonium center have been developed for the AMBER force field to permit analysis of NMR results and to enable comparison of the relative energies of the different conformations of AdoMet that have been found in crystal structures of complexes with proteins. S-Methylmethionine and S-dimethylsulfonioproprionate adopt a variety of conformations in aqueous solution; a conformation with an electrostatic interaction between the sulfonium sulfur and the carboxylate group is not noticeably favored, in contrast to the preferred conformation found by in vacuo calculations. Nuclear Overhauser effect measurements and computational results for AdoMet indicate a predominantly anti conformation about the glycosidic bond with a variety of conformations about the methionyl C-alpha-C-beta and C-beta-C-gamma bonds. An AdoMet conformation in which the positively charged sulfonium sulfur is near an electronegative oxygen in the ribose ring is common. Comparisons of NMR results for AdoMet with those for the uncharged S-adenosylhomocysteine and 5'-methylthioadenosine, and the anionic ATP, indicate that the solution conformations are not dictated mainly by molecular charge. In 20 reported structures of AdoMet-protein complexes, both anti and syn glycosidic torsional angles are found. The methionyl group typically adopts an extended conformation in complexes with enzymes that transfer the methyl group from the sulfonium center, but is more folded in complexes with proteins that do not catalyze reactions involving the sulfur and which can use the sulfonium sulfur solely as a binding site. The conformational energies of AdoMet in these crystal structures are comparable to those found for AdoMet in solution. The sulfonium sulfur is in van der Waals contact with a protein heteroatom in the structures of four proteins, which reflects an energetically favorable contact. Interactions of the sulfonium with aromatic rings are rarely observed.