Analysis of the Interaction Interfaces of the N-Terminal Domain from Pseudomonas aeruginosa MutL

VIRGINIA MIGUEL; ELISA CORREA; LUISIN DE TULIO; JOSE LUIS BARRA; CARLOS ARGARAÑA; MARCOS ARIEL VILLARREAL

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 vol. 8 p. 69907 - 69907

ismatch Repair System corrects mutations arising from DNA replication that escape from DNA polymerase proofreadingactivity. This system consists of three main proteins, MutS-L-H, responsible for lesion recognition and repair. MutL is amember of GHKL ATPase family and its ATPase cycle has been proposed to modulate MutL activity during the repairprocess. Pseudomonas aeruginosa MutL (PaMutL) contains an N-terminal (NTD) ATPase domain connected by a linker to a C-terminal (CTD) dimerization domain that possesses metal ion-dependent endonuclease activity. With the aim to identifycharacteristics that allow the PaMutL NTD allosteric control of CTD endonuclease activity, we used an in silico andexperimental approach to determine the interaction surfaces of P. aeruginosa NTD (PaNTD), and compared it with the wellcharacterized Escherichia coli MutL NTD (EcNTD). Molecular dynamics simulations of PaNTD and EcNTD bound to or free ofadenosine nucleoti