Electrostatic fingerprints of catalytically active amino acids in enzymes
Electrostatic fingerprints of catalytically active amino acids in enzymes
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DOI：
10.1002/pro.4291
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发表时间：
2022-05-01
期刊：
影响因子：
8
通讯作者：
Ondrechen, Mary Jo
中科院分区：
文献类型：
--
作者：
Iyengar, Suhasini M.;Barnsley, Kelly K.;Ondrechen, Mary Jo
本文研究了20种酶的静电和质子转移性质，这些酶代表了所有6种主要酶类和各种不同的折叠。本文报道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。本文研究的催化残基与至少一种其他的天冬氨酸残基或谷氨酸残基强偶联，并且通常与多个其他的羧酸残基偶联，其内在pK(a)差异小于1个pH单位。有时这些催化酸性残基也与组氨酸残基偶联，使得酸性残基的内在pK(a)高于组氨酸残基。本文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偶联，其中阴离子形成残基的内在pK(a)高于赖氨酸。一些催化赖氨酸也偶联到其他赖氨酸具有内在的pK(a)差异在1 pH单位内。讨论了促进亲核性的可能类型的相互作用的一些证据。本文报道的相互作用提供了重要的线索，说明溶液中游离氨基酸的弱布朗斯特德酸或碱的侧链官能团如何在酶环境中获得催化效力并成为强酸、强碱或亲核试剂。
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(a) differences less than 1 pH unit. Sometimes these catalytic acidic residues are also coupled to a histidine residue, such that the intrinsic pK(a) 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(a) of the anion-forming residue is higher than that of the lysine. Some catalytic lysines are also coupled to other lysines with intrinsic pK(a) 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 Bronsted 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.