The Retaining Mechanism of Xylose Transfer Catalyzed by Xyloside α-1,3-Xylosyltransferase (XXYLT1): a Quantum Mechanics/Molecular Mechanics Study
Abstract
Glycosyltransferases (GTs) are a ubiquitous group of enzymes that catalyze the synthesis of glycosidic bonds. In this work, we focused on the retained reaction catalyzed by xyloside α-1,3-xylosyltransferase (XXYLT1) from Mus musculus. Our calculations revealed that the xylose transfer reaction follows the SNi-like mechanism, which involves a short-lived oxocarbenium-phosphate ion-pair intermediate (IP). The previously obtained crystal structure of the UDP-Xyl ternary Michaelis reaction complex was found to be an inactive form. Accordingly, the β-phosphate oxygen O3B of the donor should first undergo a conformational change to reach an active state where the donor forms a strong hydrogen bond with the acceptor, facilitating the departure of the phosphate group. Our calculations also revealed that two predicated transition states for the sugar-phosphate bond cleavage and glycosidic bond formation are structurally similar to the short-lived intermediate, which contains a three-member ring formed by the β-phosphate oxygen, the hydroxyl oxygen in the acceptor, and the anomeric carbon. It can be considered as a typical characteristic of the SNi-like mechanism. In addition, a nearby polar residue, Q330, is responsible for stabilizing the short-lived intermediate by electrostatic interactions. Thus, the Q330A mutant can abolish the activity of XXYLT1. In addition, using UDP-glucose as the donor, our calculations revealed that glucose transfer would correspond to a higher energy…
Read the paper
Related studies
- Chaos and quantum thermalization
- The Dalton quantum chemistry program system
- Quantum dots: synthesis, bioapplications, and toxicity
- Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study
- A Guide to In Silico Drug Design
- Quantitative metabolomics by H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.