8B1I

DtpB-Nb132-MS

Summary for 8B1I

• Entry DOI: 10.2210/pdb8b1i/pdb
• Descriptor: Dipeptide and tripeptide permease B, DECANE, HEXANE, ... (12 entities in total)
• Functional Keywords: mfs, proton coupled oligopeptide transporter, membrane protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 3
• Total formula weight: 70374.17

Authors

Killer, M.,Finocchio, G.,Lei, J.,Jungnickel, K.,Kotov, V.,Steinke, J.,Bartels, K.,Strauss, J.,Dupeux, F.,Humm, A.S.,Cornaciu, I.,Marquez, J.,Pardon, E.,Steyeart, J.,Loew, C. (deposition date: 2022-09-09, release date: 2023-08-09)

Primary citation

Kotov, V.,Killer, M.,Jungnickel, K.E.J.,Lei, J.,Finocchio, G.,Steinke, J.,Bartels, K.,Strauss, J.,Dupeux, F.,Humm, A.S.,Cornaciu, I.,Marquez, J.A.,Pardon, E.,Steyaert, J.,Low, C.
Plasticity of the binding pocket in peptide transporters underpins promiscuous substrate recognition.
Cell Rep, 42:112831-112831, 2023

PubMed Abstract: Proton-dependent oligopeptide transporters (POTs) are promiscuous transporters of the major facilitator superfamily that constitute the main route of entry for a wide range of dietary peptides and orally administrated peptidomimetic drugs. Given their clinical and pathophysiological relevance, several POT homologs have been studied extensively at the structural and molecular level. However, the molecular basis of recognition and transport of diverse peptide substrates has remained elusive. We present 14 X-ray structures of the bacterial POT DtpB in complex with chemically diverse di- and tripeptides, providing novel insights into the plasticity of the conserved central binding cavity. We analyzed binding affinities for more than 80 peptides and monitored uptake by a fluorescence-based transport assay. To probe whether all 8400 natural di- and tripeptides can bind to DtpB, we employed state-of-the-art molecular docking and machine learning and conclude that peptides with compact hydrophobic residues are the best DtpB binders.

PubMed: 37467108
DOI: 10.1016/j.celrep.2023.112831

Experimental method

X-RAY DIFFRACTION (2.55 Å)