Identifying the CmbT substrates specificity by using a quantitative structure-activity relationship (QSAR) study

The results obtained in this study showed that high CmbT affinities to ethidium, sulbactam, and sulfathiazole could be related to the absence of significant unfavourable interactions. In contrast, the presence of specific unfavourable interaction between two hydrogen bond donor groups in bacitracin, apramycin, novobiocin, vancomycin, kanamycin, gentamycin, and tobramycin is found to be the main reason for their lower CmbT affinities. In addition, membrane position of the CmbT binding site and positive correlation between substrates lipophilicity (log DpH 5.0) and CmbT affinity strongly indicates that CmbT recognizes its substrates within the membrane.