Modelación molecular y variación estructural de las integrasas de dos retrovirus humanos: HTLV-I y VIH-1

Objective: To analyze the molecular characteristics and amino acid sequence variations of HTLV-I and of HIV-1 integrases and their population variants. Materials adn methods: Data mining and analysis of integrase sequences and protein structure data bases by using appropriate software for modelling and search for polymorphic substitutions in HTLV-I and HIV-1 integrase amino acid sequences previously reported. Results: HTLV-I and HIV-1 integrases are proteins of 288 amino acid residues. Structural modeling of tertiary folding of HTLV-I integrase catalytic central domain’s, showed closed structural characteristic with those of HIV-1, ASV and RSV. From 103 full amino acid sequences of HIV-1 integrase, 53 substitutions located in 46 different codons were recorded. The more frequents correspond to N27G (32,1%), L101I (31,1%), A265V (30,1%) and T123A (27,0%). None of these frequent substitutions introduced changes in the folding of HIV-1 native integrase. Conclusion: The tridimensional structure of central catalytic domain would influence the integrase activity and its relationship with potentially inhibitory molecules. Those observed amino acid substitutions were neutral and do not alter the native protein structure. Our data confirm those previously published, and enable us to propose that IN is a new and promissory target for develop more effective antiviral therapies in the XXI century.