IFIS - LITORAL   24734
Unidad Ejecutora - UE
congresos y reuniones científicas
A theoretical analysis of the conserved structural motif in the Reverse Transcriptase domain of the human telomerase protein
Santiago del Estero
Congreso; SAB2015; 2015
Institución organizadora:
Sociedad Argentina de BiofĂ­sica
Telomeraseis a ribonucleoprotein complex responsible for maintaining the length andintegrity of chromosome ends adding specific nucleotides to an existing DNAprimer having RNA as a template. It contains a reverse transcriptase (RT)domain where the reaction takes place and it is essential for the biologicalfunction. Due to the lack of an experimental structure a ribonucleoproteincomplex model was obtained, combining a Fold-Recognition model for the proteinpart, together with a double strand DNA/RNA, a dNTP (simulating the incomingdeoxinucleoside), and two Mg2+ ions (all of these taken from knownstructures of the PDB). Molecular dynamics simulation by 200 ns was used to removesteric problems and obtain a converged complex model. This complex representsthe previous step to the nucleophilic atack and formation of the phosphodiesterbond between the last nucleotide of the DNA chain and the incoming dNTP. Themolecular dynamics simulation in explicit solvent of the complex allows toobtain the correct coordination of the Mg ions, whose almost perfect octahedral coordination emergeas crucial, to place all the atoms attheir reaction positions. From this ?model of the complex? it was possible toinfer, at atomic detail, the role of some of the conserved residues among the RTprotein sequences and to identify and characterize a ?catalytic pocket? for thehuman telomerase, defined  by the nineconserved residues among these sequences.Finally, we concluded that not only the nine kyresidues are conserved in sequence but also that the catalytic pocket remainsconserved in structure for the human. Taking into account the essential roleplayed in the telomerase catalytic activity by some of these residues, wepropose that the notion of a ?catalytic site? should be revised. Instead, the?catalytic pocket? formed by the conserved residues is proposed to be as themost appropriate description of the structure needed forthe catalytic activity.