Enzyme architecture: on the importance of being in a protein cage.

Enzyme architecture: on the importance of being in a protein cage. Curr Opin Chem Biol. 2014 Mar 31;21C:1-10 Authors: Richard JP, Amyes TL, Goryanova B, Zhai X Abstract Substrate binding occludes water from the active sites of many enzymes. There is a correlation between the burden to enzymatic catalysis of deprotonation of carbon acids and the substrate immobilization at solvent-occluded active sites for ketosteroid isomerase (KSI-small burden, substrate pKa=13), triosephosphate isomerase (TIM, substrate pKa≈18) and diaminopimelate epimerase (DAP epimerase, large burden, substrate pKa≈29) catalyzed reaction. KSI binds substrates at a surface cleft, TIM binds substrate at an exposed 'cage' formed by closure of flexible loops; and, DAP epimerase binds substrate in a tight cage formed by an 'oyster-like' clamping motion of protein domains. Directed evolution of a solvent-occluded active site at a designed protein catalyst of the Kemp elimination reaction is discussed. PMID: 24699188 [PubMed - as supplied by publisher]
Source: Current Opinion in Chemical Biology - Category: Biochemistry Authors: Tags: Curr Opin Chem Biol Source Type: research