ANALYSIS OF PROTEIN-PROTEIN/PROTEIN DNA INTERFACES OF Pseudomonas aeruginosa MUTL NTERMINAL DOMAIN

MIGUEL VIRGINIA; CORREA EME; DE TULLIO L; BARRA JL; ARGARAÑA CE; VILLARREAL MA

Congreso; XLVII Reunión Anual de SAIB; 2011

Mismatch Repair System (MRS) corrects mutations arising from DNA replication that escape from DNA polymerase proofreading activity. MutL coordinates the action of most of the proteins involved in repair. MutL is a dimeric protein that contains a Cterminal (CTD) dimerization domain connected by a linker to an Nterminal (NTD) ATPase domain. MutL is a member of GHL ATPase family and the ATPase cycle has been proposed to modulate MutL´s activity during the repair process. We used an experimental and in-silico approach to determine interaction surfaces of P. aeruginosa NTD (paNTD). Unlike E. coli NTD (ecNTD), paNTD is dimeric in absence of nucleotide. Since the crystal structure of paNTD is not known, we constructed a 3D homology model. MD simulations of paNTD models and ecNTD crystal structures with or without ATP were carried out in order to analyze structural differences. Therefore, in silico analysis allowed us to identify and characterize the paNTD dimerization interface and compared it with that of ecNTD. Also, simulations in mixed solvent were performed to identify areas with a high tendency to desolvate, allowing us to identify other two putative interaction interfaces. One corresponds to the known homologue region of E. coli DNA binding patch, whereas the second interface corresponds to a potential paNTD protein-protein interaction site.