Function and mechanism of zinc metalloenzymes
Function and mechanism of zinc metalloenzymes
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DOI：
10.1093/jn/130.5.1437s
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发表时间：
2000-05-01
影响因子：
4.2
通讯作者：
Fierke, CA
中科院分区：
文献类型：
--
作者：
McCall, KA;Huang, CC;Fierke, CA
锌是超过300种酶的活性所必需的，涵盖了所有六类酶。蛋白质中的锌结合位点通常是扭曲的四面体或三角双锥几何结构，由半胱氨酸的硫、组氨酸的氮或天冬氨酸和谷氨酸的氧或组合组成。蛋白质中的锌可以直接参与化学催化，也可以对维持蛋白质结构和稳定性起重要作用。在所有催化位点中，锌离子作为刘易斯酸起作用。我们实验室的研究人员正在解剖碳酸酐酶锌结合位点中分子识别和催化的决定因素。这些研究表明，直接配体的化学性质和周围的氢键网络的结构是至关重要的碳酸酐酶的活性和锌结合位点的金属离子亲和力。对天然存在的锌结合位点的理解将有助于创造新的锌结合蛋白，并在现有蛋白质中设计新的金属位点用于新的目的，如作为金属离子生物传感器。
Zinc is required for the activity of > 300 enzymes, covering ail six classes of enzymes. Zinc binding sites in proteins are often distorted tetrahedral or trigonal bipyramidal geometry, made up of the sulfur of cysteine, the nitrogen of histidine or the oxygen of aspartate and glutamate, or a combination. Zinc in proteins can either participate directly in chemical catalysis or be important for maintaining protein structure and stability. In all catalytic sites, the zinc ion functions as a Lewis acid. Researchers in our laboratory are dissecting the determinants of molecular recognition and catalysis in the zinc-binding site of carbonic anhydrase. These studies demonstrate that the chemical nature of the direct ligands and the structure of the surrounding hydrogen bond network are crucial for both the activity of carbonic anhydrase and the metal ion affinity of the zinc-binding site. An understanding of naturally occurring zinc-binding sites will aid in creating de novo zinc-binding proteins and in designing new metal sites in existing proteins for novel purposes such as to serve as metal ion biosensors.