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Catalytic Mechanism of Cellobiohydrolase, CelS, on Cellulose Degradation

Catalytic Mechanism of Cellobiohydrolase, CelS, on Cellulose Degradation

Structure of CelS in complex with cellooligomers


by Moumita Saharay

     The anaerobic clostridium thermocellum produces an extracellular cellulase, Cellobiohydrolase CelS, which efficiently degrades cellulose by hydrolysing the glycosidic bonds. The catalytic domain of CelS in complex with substrate and product shows tunnel shaped substrate-binding region formed by the alpha helices in the protein. Enzymatic hydrolysis of the glycosidic bond takes place via general acid catalysis that requires two critical residues : a proton donor and a nucleophile/base. This process can happen with net retention or inversion of anomeric configuration. The structural analysis of CelS crystal indicates towards the inversion mechanism where the distance between the catalytic residues is significantly greater than that between the catalytic carboxylates of retaining enzymes. The hydrolysis in CelS possibly involves Glu87 as an acid to protonate the glycosidic oxygen atom and Tyr351 as a base to extract a proton from the nucleophilic water molecule that attacks the anomeric carbon atom.

     Quantum mechanical/molecular mechanical (QM/MM) molecular dynamics and free energy simulations are performed on CelS and carbohydrate complex to understand the step by step mechanism for hydrolysis of glycosidic bond in cellulose and origin of product specificity.

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