Evaluación In Silico de la actividad hidrolítica de las β-lactamasas OXA y CTX-M frente a antibióticos β-lactámicos
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Rodríguez Blanco, Ana Rosa
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Las β-lactamasas OXA y CTX-M son de amplia diseminación y confieren a las bacterias resistencia a antibióticos. Este trabajo evalúa in silico el efecto del cambio en sus secuencias en la actividad hidrolítica frente a antibióticos β-lactámicos. El análisis de secuencias por alineamiento múltiple de estas enzimas se hizo mediante Clustal-W construyéndose árboles de distancia con MEGA 5.2 por neighbor-joining. El acoplamiento molecular entre las enzimas y los antibióticos se realizó con Autodock 1.5.6. Los resultados obtenidos se sistematizaron en el sistema BLA.id. Las CTX-Ms muestran un alto grado de conservación comparadas con las OXAs que son más diversas, tanto en perfil de susceptibilidad como en secuencia. Los resultados de correlación entre la secuencia vs perfil de actividad frente a antibióticos muestran que tanto las OXAS como las CTX-Ms mantienen conservadas las secuencias del sitio activo pero presentan cambios puntuales fuera de este, que estabilizan el acoplamiento enzima-sustrato modificando el perfil de actividad hidrolítica.
Abstract. OXA and CTX-M β-lactamases are of wide dissemination on bacteria and confer them resistance to antibiotics. This work assesses in silico the effect caused in the hydrolytic activity against β-lactamic antibiotics by a change in the sequence of the enzymes. The sequence analysis by multiple alignment of the enzymes was done using Clustal-W, building distance trees by neighbor-joining with MEGA 5.2. The molecular coupling between the enzymes and the antibiotics was done with Autodock 1.5.6. The results were uploaded to the BLA.id system. CTX-Ms show a high degree of conservation in comparison with OXAs which are more diverse both in susceptibility profile and in sequence. Correlation results between sequence vs activity profile show that both OXAs and CTX-Ms keep conserved the sequences of the active site but show specific changes outside of it that stabilize the coupling enzyme-substrate modifying the hydrolytic activity profile.
Abstract. OXA and CTX-M β-lactamases are of wide dissemination on bacteria and confer them resistance to antibiotics. This work assesses in silico the effect caused in the hydrolytic activity against β-lactamic antibiotics by a change in the sequence of the enzymes. The sequence analysis by multiple alignment of the enzymes was done using Clustal-W, building distance trees by neighbor-joining with MEGA 5.2. The molecular coupling between the enzymes and the antibiotics was done with Autodock 1.5.6. The results were uploaded to the BLA.id system. CTX-Ms show a high degree of conservation in comparison with OXAs which are more diverse both in susceptibility profile and in sequence. Correlation results between sequence vs activity profile show that both OXAs and CTX-Ms keep conserved the sequences of the active site but show specific changes outside of it that stabilize the coupling enzyme-substrate modifying the hydrolytic activity profile.