Characterization of aromatic-thiol π-type hydrogen bonding and phenylalanine-cysteine side chain interactions through ab initio calculations and protein database analyses
Characterization of aromatic-thiol π-type hydrogen bonding and phenylalanine-cysteine side chain interactions through ab initio calculations and protein database analyses
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DOI：
10.1080/00268970110063917
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发表时间：
2001-10-01
影响因子：
1.7
通讯作者：
Weaver, DF
中科院分区：
文献类型：
--
作者：
Duan, GL;Smith, VH;Weaver, DF
在本研究中，通过C6H6-HSCH3模型络合物的分子轨道计算和609个X射线蛋白质结构的数据库分析，表征了芳香-硫醇pi氢键和苯丙氨酸-半胱氨酸侧链相互作用。芳香-硫醇pi氢键相互作用的稳定能为2.60千卡·摩尔(-1)，比已报道的芳香-羟基和芳香-氨基氢键更强。然而，芳香-硫醇氢键的出现在蛋白质中是相当罕见的。这是因为大多数硫醇基团参与了二硫键或更强的S-H的形成。。O(或N)在蛋白质环境中的“正常”氢键。苯丙氨酸侧链与半胱氨酸残基之间的相互作用表现为苯基(Phe)-(HSCH2-)(Cys)相互作用。这种相互作用的成键能约为3.71千卡摩尔(-1)，并且是以最佳的苯基(Phe)-(HS-)(Cys)pI型氢键相互作用的几何排列实现的。这种相互作用对硫原子上两个孤电子对相对于苯环的p电子云的取向非常敏感。因此，能够实现显著成键能量的相互作用构型仅存在于狭窄的构型空间内。对609个实验X射线蛋白质结构的数据库分析表明，1620个半胱氨酸残基中只有268个涉及苯丙氨酸-半胱氨酸侧链相互作用。这些相互作用大多以pi(芳香)-孤对(硫)吸引的形式发生，对应的成键能小于1.5kcal摩尔(-1)。少数化合物为芳香-硫醇氢键，键能为2.0-3.6kcal摩尔(-1)。
In this study, the aromatic-thiol pi hydrogen bonding and phenylalanine-cysteine side chain interactions are characterized through both molecular orbital calculations on a C6H6-HSCH3 model complex and database analyses of 609 X-ray protein structures. The aromatic-thiol pi hydrogen bonding interaction can achieve a stabilization energy of 2.60 kcal mol(-1), and is stronger than the already documented aromatic-hydroxyl and aromatic-amino hydrogen bonds. However, the occurrence of the aromatic-thiol hydrogen bond is rather rare in proteins. This is because most of the thiol groups participate in the formation of either disulphide bonds or stronger S-H . . .O (or N) 'normal' hydrogen bonds in a protein environment. Interactions between the side chains of phenylalanine and cysteine residues are characterized as the phenyl( Phe)-(HSCH2-)(Cys) interaction. The bonding energy for such interactions is approximately 3.71 kcal mol(-1) and is achieved in a geometric arrangement with an optimal phenyl(Phe)-(HS-)(Cys) pi -type hydrogen bonding interaction. The interaction is very sensitive to the orientation of the two lone electron pairs on the sulphur atom relative to the p electron cloud of the phenyl ring. Accordingly, the interaction configurations that can accomplish a significant bonding energy exist only within a narrow configurational space. The database analysis of 609 experimental X-ray protein structures demonstrates that only 268 of the 1620 cysteine residues involve such phenylalanine-cysteine side chain interactions. Most of these interactions occur in the form of pi (aromatic)-lone pair(sulphur) attractions, and correspond to a bonding energy less than 1.5 kcal mol(-1). A few were identified as the aromatic-thiol hydrogen bond with a bonding energy of 2.0-3.6 kcal mol(-1).