Binding modes of decavanadate to myosin and inhibition of the actomyosin ATPase...

• Author(s): Tiago, Teresa ; Martel, Paulo ; Gutiérrez-Merino, Carlos ; Aureliano, M.
• Date: 2007
• Persistent ID: http://hdl.handle.net/10400.1/1298
• Origin: Sapientia - Universidade do Algarve
• Subject(s): Myosin; Decavanadate
• Document Type: Article
• Language: English

Description

Decavanadate, a vanadate oligomer, is known to interact with myosin and to inhibit the ATPase activity, but the putative binding sites and the mechanism of inhibition are still to be clarified. We have previously proposed that the decavanadate (V10O28 6−) inhibition of the actin-stimulated myosin ATPase activity is non-competitive towards both actin and ATP. A likely explanation for these results is that V10 binds to the so-called back-door at the end of the Pi-tube opposite to the nucleotide-binding site. In order to further investigate this possibility, we have carried out molecular docking simulations of the V10 oligomer on three different structures of the myosin motor domain of Dictyostelium discoideum, representing distinct states of the ATPase cycle. The results indicate a clear preference of V10 to bind at the back-door, but only on the “open” structures where there is access to the phosphate binding-loop. It is suggested that V10 acts as a “back-door stop” blocking the closure of the 50- kDa cleft necessary to carry out ATP-γ-phosphate hydrolysis. This provides a simple explanation to the non-competitive behavior of V10 and spurs the use of the oligomer as a tool to elucidate myosin back-door conformational changes in the process of muscle contraction.