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首页> 外文期刊>Polyhedron: The International Journal for Inorganic and Organometallic Chemistry >Conformational studies of 5 '-deoxyadenosyl-13-epicobalamin, a coenzymatically active structural analog of coenzyme B-12
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Conformational studies of 5 '-deoxyadenosyl-13-epicobalamin, a coenzymatically active structural analog of coenzyme B-12

机译：5'-脱氧腺苷-13-表阿巴巴林的构象研究，一种辅酶B-12的辅酶活性结构类似物

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5'-Deoxyadenosyl-13-epicobalamin(Ado-13-epiCbl) is a coenzymatically active structural analog of coenzyme B-12 (5'-deoxyadenosylcobalamin, AdoCbl) in which epimerization at the corrin ring C13 places the e propionamide side chain in an "upwardly" axial position. This would seem to-bring the e side chain into direct steric contact with the adenosyl (Ado) moiety in its normal "southern" conformation (with the purine above the C ring) seen in the solid state for AdoCbl. Molecular mechanics calculations show that this conformation is the global minimum for AdoCbl, but that three other conformations represent local minima, including a "western", a "northern", and an "eastern" conformation, the last of which is known to be populated at room temperature from NMR studies. A structure for Ado-13-epiCbl has been generated by molecular dynamics/simulated annealing calculations starting from the-neutron diffraction coordinates for AdoCbl after epimerization at C13. Molecular mechanics calculations on the resulting structure show that a "western" conformation is the global minimum, but that three other conformations, a "northern", an "eastern", and a "northeastern", are of relatively low energy and separated by relatively low energy barriers. The traditional "southern" conformation does not appear as a local energy minimum and is some 6 kcal mol(-1) destabilized relative to the global minimum due to geometric distortions to relieve steric strain. Two-dimensional homonuclear NMR experiments show extraordinary conformational flexibility in Ado-13-epiCbl with 21 NOE crosspeaks between Ado protons and non-Ado protons, 50% more than in AdoCbl itself. Together with the calculated,geometries for the four Ado-13-epiCbl conformers, these data suggest that at least three, and possibly all four of the conformers are populated at room temperature, in contrast to AdoCbl. in which only the "southern" and "eastern" conformers are populated under these conditions. Considering the enzymology of Ado-13-epiCbl, the inaccessibility of its "southern" conformation, ana the activity of other AdoCbl analogs structurally modified in the Ado moiety, it is suggested that it may well be the "eastern" conformation, accessible to both AdoCbl and Ado-13-epiCbl, which is enzymatically active. (C) 1998 Elsevier Science Ltd. Ah rights reserved. [References: 72]
机译：5'-脱氧腺苷基-13-表巴巴林蛋白（Ado-13-epiCbl）是辅酶B-12（5'-脱氧腺苷基钴胺素，AdoCbl）的辅酶活性结构类似物，其中在柯林环C13上的差向异构化将丙酰胺酰胺侧链置于“向上”轴向位置。这似乎使处于固态的AdoCbl的e侧链与腺苷（Ado）部分以其正常的“南部”构象（嘌呤在C环上方）直接与空间接触。分子力学计算表明，这种构象是AdoCbl的整体最小值，但是其他三个构象代表局部最小值，包括“西方”构象，“北方”构象和“东方”构象，已知最后一个构象是填充的NMR研究表明在室温下Ado-13-epiCbl的结构已经通过分子动力学/模拟退火计算从C13异构化后的AdoCbl的中子衍射坐标开始生成。对所得结构的分子力学计算表明，“西方”构象是整体最小值，但是其他三个构象“北”，“东”和“北”构象的能量相对较低，并且被相对分离低能垒。传统的“南部”构象不会显示为局部能量最小值，并且相对于全局最小值而言，约有6 kcal mol（-1）不稳定，这是由于几何变形以减轻空间应变而引起的。二维同核NMR实验显示，Ado-13-epiCbl在Ado质子和非Ado质子之间具有21个NOE交叉峰，具有非凡的构象灵活性，比AdoCbl本身高50％。连同所计算的四个Ado-13-epiCbl构象异构体的几何形状一起，这些数据表明，与AdoCbl相比，至少三个，可能是全部四个构象异构体在室温下分布。在这些条件下，仅填充“南部”和“东部”构象体。考虑到Ado-13-epiCbl的酶学，其“南部”构象的不可及性以及在Ado部分进行结构修饰的其他AdoCbl类似物的活性，建议它很可能是“东部”构象，两者AdoCbl和Ado-13-epiCbl具有酶活性。 （C）1998 Elsevier Science Ltd.版权所有。 [参考：72]

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