engleski

Human DPP III - Keap1 interactions

Kelch-like ECH associated protein (Keap1) is a cellular sensor for oxidative stress and a negative regulator of the nuclear erythroid 2–related factor 2 (Nrf2). A cytosollic metallopeptidase dipeptidyl peptidase III (DPP III) has been shown to interact with the Kelch domain of Keap1 via the ETGE motif located in a flexible loop belonging to the upper domain. Using the previously developed models of the DPP III - Keap1 complex, we are trying to identify the conformation of the ETGE- containing loop in the complex, as well as the work required to achieve the active conformation for Keap1 binding. Although the DPP III - Keap1 interaction through the conserved ETGE motif has been experimentally confirmed, the extensive MD simulations of the human DPP suggest that the loop is attached to the upper domain of DPP III at all times. In order to quantify the thermodynamic barrier and the work required for the loop translocation , as well as the subsequent complex formation we have used steered MD simulations, adaptive steered MD simulations and conventional MD simulations in conjunction with the MM-PBSA energy calculations.

Keap1 ; DPP III ; dipeptidyl peptidase III

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