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What regulates the catalytic activities in AGEs catalysis? An answer from the quantum mechanics/molecular mechanics simulations

Abstract

The AGE superfamily (AGEs) is a kind of isomerase which is very important in either physiologically or 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, the results for the epimerization activity catalysed by RaCE and the isomerization activity catalysed by SeYihS were presented 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. It makes that the pathways of ring opening catalysed by them are similar. However, one non-conserved residue (Leu183 in RaCE, Met175 in SeYihS) in the active site, which different in steric hindrance, causes a small but effective change in the direction of ring opening in the stage 1. And then, this change will induce the fundamentally different catalytic activity for RaCE and SeYihS in the stage 2. Our results proposed a novel viewpoint about the regulatory mechanism between CE and YihS in AGEs, and it may be helpful for further experiments of rational enzyme-design based on the (α/α)6-barrel basic scaffold.

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Publication details

The article was received on 17 Oct 2017, accepted on 10 Nov 2017 and first published on 10 Nov 2017


Article type: Paper
DOI: 10.1039/C7CP07079A
Citation: Phys. Chem. Chem. Phys., 2017, Accepted Manuscript
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    What regulates the catalytic activities in AGEs catalysis? An answer from the quantum mechanics/molecular mechanics simulations

    Y. Zhang, H. Zhang and Q. Zheng, Phys. Chem. Chem. Phys., 2017, Accepted Manuscript , DOI: 10.1039/C7CP07079A

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