Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
Eur Biophys J. 2012 May;41(5):449-60. doi: 10.1007/s00249-012-0798-4. Epub 2012 Apr 7.
Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1,072 Å(3). The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes.
通过现代计算几何程序，可以很好地定义具有已知结构的酶的催化活性部位。使用 CASTp 程序定义并测量了 Catalytic Site Atlas 数据库中 573 种酶的催化活性部位的体积。这些活性部位被认为是催化活性的，因为它们所含的氨基酸已知参与酶催化的化学反应。酸和碱基侧链是催化活性部位的可靠标记。催化活性部位有 4 个酸侧链和 5 个碱侧链，平均体积为 1072Å(3)。酸侧链的数密度为 8.3M（化学单位）；碱基侧链的数密度为 10.6M。这些酶的催化活性部位是一种不寻常的静电和空间环境，其中侧链和反应物拥挤在一起，混合物更像是离子液体而不是理想的无限稀释溶液。反应物和侧链的静电和拥挤情况似乎对催化功能很重要。在三种类似的离子通道中，对拥挤电荷的模拟解释了在广泛的溶液和浓度范围内测量的选择性的主要性质。在构建酶的催化活性部位模型时，明智的做法是使用设计用于研究相互作用的复杂流体的数学方法。
