AI Article Synopsis
- The enzyme UDP-galactopyranose mutase (UGM) is a potential target for drugs aimed at treating infections caused by Trypanosoma cruzi.
- Researchers used Umbrella Sampling simulations to analyze how UDP-galactopyranose is released from UGM, uncovering key conformational changes in both the substrate and enzyme.
- They discovered that the galactopyranose part of the substrate is very mobile and that the active site undergoes a multi-stage opening/closing process, revealing uncharacterized interactions with important conserved residues, aiding drug design.
Article Abstract
The enzyme UDP-galactopyranose mutase (UGM) represents a promising drug target for the treatment of infections with Trypanosoma cruzi. We have computed the Potential of Mean Force for the release of UDP-galactopyranose from UGM, using Umbrella Sampling simulations. The simulations revealed the conformational changes that both substrate and enzyme undergo during the process. It was determined that the galactopyranose portion of the substrate is highly mobile and that the opening/closing of the active site occurs in stages. Previously uncharacterized interactions with highly conserved residues were also identified. These findings provide new pieces of information that contribute to the rational design of drugs against T. cruzi.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441589 | PMC |
| http://dx.doi.org/10.1021/acs.jcim.8b00675 | DOI Listing |
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