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Predicting antibiotic resistance de novo

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Fowler Lab
Fowler Lab

Predicting antibiotic resistance de novo

New Publication: The Extra-Cellular Domain of PepT1 and PepT2

Philip Fowler, 2nd November 2015

PepT1 is a nutrient transporter found in the cells that line your small intestine. It is not only responsible for the uptake of di- and tai-peptides, and therefore much of your dietary proteins, but also the uptake of most β-lactam antibiotics. This serendipity ensures that we can take (many of) these important drugs orally.

Our ultimate goal is to develop the capability to predict modifications to drug scaffolds that will improve or enable their uptake by PepT1, thereby improving their oral bioavailability.

In Structure we report the structures of the extra-cellular domains (ECDs) of PepT1 and PepT2. This is an important milestone on the road to elucidating a structure of PepT1 and allows us to propose the first full-length structural model of PepT1 (see above). Intriguingly, the data also suggests that the ECD also interacts with trypsin, thereby increasing the local concentration of peptides around the transporter, improving its efficiency.

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