Chondrotinase Abc I Thermal Stability Is Enhanced by Site-Directed Mutagenesis: A Molecular Dynamic Simulations Approach Publisher Pubmed



Bagherzadeh K^{1, 2} ; Maleki M³ ; Golestani A³ ; Khajeh K⁴ ; Amanlou M² Show Affiliations
Source: Journal of Biomolecular Structure and Dynamics Published:2018

Abstract

Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of growth in the adult central nervous system. Use of the enzyme chondroitinase ABC I (ChABC I) as a strategy to reduce CSPG inhibition in experimental models of spinal cord injury has led to observations of its remarkable capacity for repair. More importantly, ChABC therapy has been demonstrated to promote significant recovery of function to spinal injured animals. Despite this incomparable function of ChABC I, its clinical application has been limited because of its thermal instability as reported in the literature. In a recent study by Nazari-Robati et al., thermal stability of ChABC I was improved by protein engineering using site-directed mutagenesis method. Here, in this study, molecular dynamics simulations were used to take a closer look into the phenomenon leading to the experimentally observed thermal stability improvement followed by the corresponding site-directed mutagenesis. We concluded that the mutations induce local flexibility along with a re-conformation into the native structure which consequently increase the protein thermal stability. © 2017 Informa UK Limited, trading as Taylor & Francis Group.