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

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.

SUBMITTER: Richard JP

PROVIDER: S-EPMC4149950 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Richard John P JP Amyes Tina L TL Goryanova Bogdana B Zhai Xiang X

Current opinion in chemical biology 20140331

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 ...[more]

PMID: 24699188

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