Molecular insight into the inhibition mechanism of cyrtominetin to α-hemolysin by molecular dynamics simulation

The protein alpha-hemolysin (alpha-HL) is a self-assembling exotoxin that binds to the membrane of a susceptible host cell. In this paper, experimental studies show that cyrtominetin (CTM) can inhibit the hemolytic activity of alpha-HL To understand how CTM can affect hemolytic activity, molecular dynamics simulations were carried out for alpha-HL CTM complex and these results were compared with the crystal structure of monomeric alpha-HL. With this approach, the analysis revealed that the inhibition of CTM involves CTM directly binding to alpha-HL Due to the binding of CTM, the conformation of the critical Loop region was restrained. This mechanism was confirmed by the experimental data. These findings indicate that CTM hinders the lysis activity of alpha-HL through a novel mechanism. (C) 2013 Elsevier Masson SAS. All rights reserved.