Prediction of the Closed Conformation and Insights into the Mechanism of the Membrane Enzyme LpxR
Biophysical Journal, ISSN: 0006-3495, Vol: 115, Issue: 8, Page: 1445-1456
2018
- 4Citations
- 19Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations4
- Citation Indexes4
- CrossRef4
- Captures19
- Readers19
- 19
Article Description
Covalent modification of outer membrane lipids of Gram-negative bacteria can impact the ability of the bacterium to develop resistance to antibiotics as well as modulating the immune response of the host. The enzyme LpxR from Salmonella typhimurium is known to deacylate lipopolysaccharide molecules of the outer membrane; however, the mechanism of action is unknown. Here, we employ molecular dynamics and Monte Carlo simulations to study the conformational dynamics and substrate binding of LpxR in representative outer membrane models as well as detergent micelles. We examine the roles of conserved residues and provide an understanding of how LpxR binds its substrate. Our simulations predict that the catalytic H122 must be N ε -protonated for a single water molecule to occupy the space between it and the scissile bond, with a free binding energy of −8.5 kcal mol −1. Furthermore, simulations of the protein within a micelle enable us to predict the structure of the putative “closed” protein. Our results highlight the need for including dynamics, a representative environment, and the consideration of multiple tautomeric and rotameric states of key residues in mechanistic studies; static structures alone do not tell the full story.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0006349518310269; http://dx.doi.org/10.1016/j.bpj.2018.09.002; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85054075347&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/30287112; https://linkinghub.elsevier.com/retrieve/pii/S0006349518310269; https://dx.doi.org/10.1016/j.bpj.2018.09.002
Elsevier BV
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