Conformation dependence of pKa:: Ab initio and DFT investigation of histidine
Conformation dependence of pKa:: Ab initio and DFT investigation of histidine
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DOI：
10.1021/jp048964q
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发表时间：
2004-07-22
影响因子：
2.9
通讯作者：
Perczel, A
中科院分区：
文献类型：
--
作者：
Hudáky, P;Perczel, A
发现N-甲酰基-L-组氨酸酰胺的质子亲和力和pK（a）值作为其主链和/或侧链取向的函数而变化。结构相似的构象异构体的阳离子和中性形式之间的质子亲和力在-246和-230 kcal mol（-1）之间，而与相同构象异构体相关的pK（a）值在6和8之间。对于中性到阴离子的转变，计算出以下范围为-342 > PA > -350 kcal mol（-1）和18 < pK（α）< 22。蛋白质表面上组氨酸的质子化状态主要取决于pH。由于质子化或去质子化，这些组氨酸残基的侧链和/或主链取向可能会发生相当大的变化。实例提出并确认从头计算，在不同的pH值条件下，蛋白质结晶，导致在相同的组氨酸残基，采用不同的构象。此外，一个假设是质子化诱导的构象修饰的组氨酸残基的催化三联体的胰凝乳蛋白酶在催化过程中，这降低了pK（a）值的催化组氨酸由1.2个单位。实验和理论结果都支持质子亲和力以及组氨酸残基的pK（a）值具有强烈的构象依赖性。
Proton affinity and pK(a) values of N-formyl-L-histidinamide are found to vary as a function of its backbone and/or side-chain orientation. Proton affinities between the cationic and neutral forms of structurally similar conformers are between -246 and -230 kcal mol(-1), while pK(a) values associated with the same conformers are between 6 and 8. For the neutral-to-anion transition, the following ranges were computed -342 > PA > -350 kcal mol(-1) and 18 < pK(a) < 22. The protonation state of histidines on the surface of a protein depends primarily on the pH. Due to protonation or deprotonation, the side-chain and/or backbone orientation of these histidine residues may undergo considerable changes. Examples are presented and confirmed by ab initio calculations, where proteins were crystallized under various pH conditions, resulting in the same histidine residue to adopt different conformations. Furthermore, a hypothesis is given for a protonation-induced conformational modification of the histidine residue in the catalytic triad of chymotrypsin during catalysis, which lowers the pK(a) value of the catalytic histidine by 1.2 units. Both the experimental and theoretical results support that proton affinity as well as that pK(a) values of histidine residues are strongly conformationally dependent.