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Curr Opin Chem Biol. 2014 Aug;21:1-10. doi: 10.1016/j.cbpa.2014.03.001. Epub 2014 Mar 31.

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

Author information

  • 1Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260-3000, USA. Electronic address: jrichard@buffalo.edu.
  • 2Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260-3000, USA.

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
PMCID:
PMC4149950
DOI:
10.1016/j.cbpa.2014.03.001
[PubMed - indexed for MEDLINE]
Free PMC Article
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