Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA.
Protein Sci. 2022 May;31(5):e4291. doi: 10.1002/pro.4291.
The computed electrostatic and proton transfer properties are studied for 20 enzymes that represent all six major enzyme commission classes and a variety of different folds. The properties of aspartate, glutamate, and lysine residues that have been previously experimentally determined to be catalytically active are reported. The catalytic aspartate and glutamate residues studied here are strongly coupled to at least one other aspartate or glutamate residue and often to multiple other carboxylate residues with intrinsic pK differences less than 1 pH unit. Sometimes these catalytic acidic residues are also coupled to a histidine residue, such that the intrinsic pK of the acidic residue is higher than that of the histidine. All catalytic lysine residues studied here are strongly coupled to tyrosine or cysteine residues, wherein the intrinsic pK of the anion-forming residue is higher than that of the lysine. Some catalytic lysines are also coupled to other lysines with intrinsic pK differences within 1 pH unit. Some evidence of the possible types of interactions that facilitate nucleophilicity is discussed. The interactions reported here provide important clues about how side chain functional groups that are weak Brønsted acids or bases for the free amino acid in solution can achieve catalytic potency and become strong acids, bases or nucleophiles in the enzymatic environment.
计算静电和质子转移性质研究了 20 种酶，这些酶代表了所有六大酶类委员会和各种不同的折叠。报告了先前实验确定具有催化活性的天冬氨酸、谷氨酸和赖氨酸残基的性质。这里研究的催化天冬氨酸和谷氨酸残基与至少一个其他天冬氨酸或谷氨酸残基强烈耦合，并且通常与多个其他具有内在 pK 差异小于 1 pH 单位的羧酸盐残基耦合。有时这些催化酸性残基也与组氨酸残基耦合，使得酸性残基的固有 pK 高于组氨酸。这里研究的所有催化赖氨酸残基都与酪氨酸或半胱氨酸残基强烈耦合，其中阴离子形成残基的固有 pK 高于赖氨酸。一些催化赖氨酸残基也与内在 pK 差异在 1 pH 单位内的其他赖氨酸残基耦合。讨论了一些有助于亲核性的可能类型相互作用的证据。这里报道的相互作用为侧链功能基团如何在溶液中作为游离氨基酸的弱布朗斯特酸或碱实现催化效力，并在酶环境中成为强酸、强碱或亲核试剂提供了重要线索。
