Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY, 11439, USA.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY, 11439, USA.
Biochimie. 2020 Mar;170:65-72. doi: 10.1016/j.biochi.2019.12.009. Epub 2019 Dec 17.
We propose a new model for prochirality that satisfies all known examples: the prochiral plane. This plane contains the prochiral carbon and defines two separate faces for chemical modification. We extend this to enzyme catalysis, replacing the "three point attachment" hypothesis and its variants. Once a prochiral substrate is fixed on an enzyme surface, the asymmetry of the enzyme provides reactants exclusively on one side of the prochiral plane, producing an enantiomerically pure chiral product. The aconitase reaction is detailed as an example, using molecular modeling and its known enzymatic mechanism. We show that the prochiral substrate for this enzyme is not citrate, but rather cis-aconitate. The number of interaction points of cis-aconitate is not relevant to prochirality, but rather to substrate specificity. A second detailed example is the enzyme fumarase; here the substrate fumarate has only two binding sites, but is nonetheless fixed onto the enzyme and has a defined prochiral plane. We also provide a literature survey of more prochiral substrates, all of which have sp hybridized carbon and contain a prochiral plane. An example of a prochiral unnatural substrate for sphingosine kinase 2, fingolimod, has an sp hybridized prochiral carbon and also contains a prochiral plane. Finally, we provide an intuitive example of a prochiral physical object, a coffee cup, interacting with one hand and lip.
我们提出了一个新的前手性模型，它满足了所有已知的例子：前手性平面。这个平面包含前手性碳原子，并定义了两个可供化学修饰的独立面。我们将其扩展到酶催化中，取代了“三点附着”假说及其变体。一旦前手性底物固定在酶表面上，酶的不对称性就会将反应物专门提供给前手性平面的一侧，从而产生对映体纯的手性产物。以 aconitase 反应为例，使用分子建模及其已知的酶促机制进行详细说明。我们表明，该酶的前手性底物不是柠檬酸，而是顺式 aconitate。顺式 aconitate 的相互作用点的数量与前手性无关，而是与底物特异性有关。第二个详细的例子是酶延胡索酸酶；在这里，底物延胡索酸只有两个结合位点，但仍然固定在酶上，并具有定义明确的前手性平面。我们还提供了更多前手性底物的文献综述，所有这些底物都具有 sp 杂化碳，并包含前手性平面。sphingosine kinase 2 的前手性非天然底物 fingolimod 的一个例子，具有 sp 杂化的前手性碳原子，并且也包含一个前手性平面。最后，我们提供了一个直观的前手性物理物体的例子，即咖啡杯，与一只手和嘴唇相互作用。
