What regulates the catalytic activities in AGE catalysis? An answer from quantum mechanics/molecular mechanics simulationsElectronic supplementary information (ESI) available: The QM regions for RaCE and SeYihS (Fig. S1), total potential energy and total energy results of RaCE and SeYihS (Fig. S2), the substrate access channel analysis for RaCE and SeYihS (Fig. S3), the average distances between catalytic residues and the substrate (Table S1). See DOI: 10.1039/c7cp07079a

• Main Authors: Zhang, Yulai, Zhang, Hongxing, Zheng, Qingchuan
• Format: Article
• Language: English
• ISSN: 1463-9076; 1463-9084
• DOI: 10.1039/c7cp07079a

The AGE superfamily (AGEs) is made up of kinds of isomerase which are very important both physiologically and industrially. One of the most intriguing aspects of AGEs has to do with the mechanism that regulates their activities in single conserved active pocket. In order to clarify the relationship among single conserved active pocket and two activities in AGEs, results for the epimerization activity catalyzed by Ra CE and the isomerization activity catalyzed by Se YihS were obtained by using QM/MM umbrella sampling simulations and 2D-FES calculations. Our results show that both of them have similar enzyme-substrate combination mode for inner pyranose ring in single conserved active pocket even though they have different substrate specificity. This means that the pathways of ring opening catalyzed by them are similar. However, one non-conserved residue (Leu183 in Ra CE, Met175 in Se YihS) in the active site, which has different steric hindrance, causes a small but effective change in the direction of ring opening in stage 1. And then this change will induce a fundamentally different catalytic activity for Ra CE and Se YihS in stage 2. Our results give a novel viewpoint about the regulatory mechanism between CE and YihS in AGEs, and may be helpful for further experiments of rational enzyme design based on the (α/α) 6 -barrel basic scaffold. Our results give a novel viewpoint about the regulatory mechanism between two activities in the AGE family.