Enlightening the multifarious attributes of the Escherichia coli Sap transport system: a computational perspective

Antimicrobial peptides (AMPs) are majorly utilized by the hosts to clear off the invading bacterial pathogens. The AMPs help in the clearance of bacterial pathogens primarily by disrupting their membrane homeostasis. However, most Gram-negative pathogens have developed multiple machineries, enabling them to resist the action of AMPs. One such machinery is the sensitivity to the antimicrobial peptides (Sap) transport system. The Sap system belongs to the ATP-binding cassette (ABC) transporters and consists of five components, viz. SapABCDF. It is reported that it uptakes AMPs inside the cell that are proteolytically degraded by proteases. In contrast, in Escherichia coli, the Sap (EcSap) transport system was suggested as a putrescine exporter. In this study, with the aid of computational biological approaches, the functional prospects of the EcSap transporter were investigated. The results of this study suggest that the protein EcSapA can bind dipeptides having aromatic amino acids. Further, it can bind to oligopeptides, including AMPs. AMPs such as protamine and protegrin-1 show binding to the protein EcSapA. In addition, the molecule heme shows binding affinity toward the protein EcSapA. In summary, EcSapA seems to be involved in the uptake of a wide range of molecules, such as dipeptides, AMPs and heme. The results of this study can be utilized to design inhibitors targeting the protein SapA, as inhibiting this protein may render the bacterial system sensitive to the attacking AMPs, hence allowing the host machinery to clear off the invading pathogen. EcSapA demonstrates a dipeptide-binding affinity consisting of aromatic amino acids.The volume and spatial arrangement of the EcSapA binding site reveal the possibility of binding larger peptides.EcSapA shows affinity toward protamine and protegrin-1.Further, EcSapA displays binding toward heme molecules.The transmembrane domains of the EcSap transport system possess a topology similar to the ABC importers. EcSapA demonstrates a dipeptide-binding affinity consisting of aromatic amino acids. The volume and spatial arrangement of the EcSapA binding site reveal the possibility of binding larger peptides. EcSapA shows affinity toward protamine and protegrin-1. Further, EcSapA displays binding toward heme molecules. The transmembrane domains of the EcSap transport system possess a topology similar to the ABC importers.