Active Site Flexibility as a Hallmark for Efficient PET Degradation by I. sakaiensis PETase

Abstract

PET (polyethylene terephthalate) is one of the most consumed synthetic polymers, with an annual production of 50 million tons. Unfortunately, PET accumulates as waste and is highly resistant to biodegradation. Recently, some fungal and bacterial thermophilic hydrolases were found to catalyze PET hydrolysis, but most of them have optimal activities at high temperatures. Strikingly, an enzyme from Ideonella sakaiensis termed PETase was described to efficiently degrade PET at room temperature, but the molecular basis of its activity is not understood. Here, a crystal structure of PETase at 2.02 Å was obtained and used in molecular dynamics at 298K,simulations showing that the active site of PETase has higher flexibility than its thermophilic counterparts. Docking analysis showed that, albeit having a similar binding affinity than other enzymes , PET binds on a different conformation onto PETase. These factors enable a closer proximity between the ester bond to be hydrolyzed and the catalytic serine. Our results are valuable for rational design endeavors aiming at increasing the efficiency of PETase andor similar enzymes even further.