CONFORMATIONAL MOBILITY IN THIAMIN AND RELATED-COMPOUNDS STUDIED BY C-13 MAGNETIC-RELAXATION
CONFORMATIONAL MOBILITY IN THIAMIN AND RELATED-COMPOUNDS STUDIED BY C-13 MAGNETIC-RELAXATION
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DOI：
10.1111/j.1749-6632.1982.tb31187.x
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发表时间：
1982-01-01
影响因子：
5.2
通讯作者：
SABLE, HZ
中科院分区：
文献类型：
--
作者：
GALLO, AA;SABLE, HZ
在以前的出版物中，我们已经关注了硫胺素和硫胺素磷酸盐化学的许多方面，我们对这些化合物在溶液中的构象特别感兴趣。焦磷酸硫胺素（硫胺素-PP）的构象，特别是嘧啶和噻唑环的相对位置，似乎对其催化功能至关重要，因为小的空间扰动会导致催化活性大大降低。硫胺素及其衍生物有三种构象，分别命名为S、F、V构象。在硫胺素、它的C-2加合物、它的磷酸酯和它与各种金属离子络合物的盐的晶体结构中，已经观察到了S（4，=+ Oo，qj，=+ 90）形式（图1）。当在C-2上有取代基时，S形式被认为是硫胺素的特征，而当C-2未被取代时，F形式是硫胺素的特征。然而，在其他研究中，发现硫胺素根据浓度的不同以S或F形式结晶。根据他对辅酶类似物与丙酮酸脱羧酶结合的研究，Schellenberger提出了"V构象（9，=+ 90，&=+ 90）“作为硫胺素-PP的活性构象。在该构象中，4 '-氨基位于噻唑鎓环的活性C-2位置附近，他提出这两个位点的相互作用可能参与硫胺素-PP催化。Biaglow等人也提出了硫胺素的V构象。这些作者发现，硫胺素的嘧啶环和噻唑鎓环都可以参与7 r-7 r与吲哚的相互作用，从而使硫胺素上的正电荷离域。为了解释溶液中吲哚与硫胺素两个环相互作用的细节，他们将硫胺素描绘成V构象。“
In previous publications we have been concerned with a number of aspects of the chemistry of thiamin and thiamin phosphates, and we have had a particular interest in the conformations of these compounds in solution. The conformation of thiamin pyrophosphate (thiamin-PP) and especially the relative positions of the pyrimidine and thiazolium rings, appears to be of critical importance for its catalytic function since small steric perturbations lead to much reduced catalytic activity.” Three conformations of thiamin and its derivatives have been proposed and are designated the S, F, V conformations. t4 The S (4,=+ Oo, qj,,=+ 90) forms (FIGURE 1) have been observed in the crystal structures of thiamin, its C-2 adducts, its phosphate esters, and its salts with various metal ion complexes.-The S form is proposed to be characteristic of thiamin when there is a substituent at C-2 and the F form is characteristic of thiamin when C-2 is unsubstituted. However, in other studies, thiamin has been found to crystallize in either the S or F form depending on the co~ nterion.’*~On the basis of his studies of binding of coenzyme analogues to pyruvate decarboxylase, Schellenberger has proposed’the V conformation (9,=+ 90, &=+ 90) as the active conformation of thiamin-PP. In that conformation the 4 ‘-amino group is placed near the reactive C-2 position of the thiazolium ring and he proposed that the interaction of these two sites may be involved in thiamin-PP catalysis. Biaglow et aL9 also suggested a V conformation for thiamin. These authors found that both the pyrimidine and thiazolium rings of thiamin could be involved in 7r-7r interactions with indoles, which serve to delocalize the positive charge on thiamin. In order to account for the details of the interaction of the indoles with both rings of thiamin in solution, they pictured thiamin as assuming a V conformation.“