Enzyme architecture: on the importance of being in a protein cage.
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.
Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260-3000, USA. Electronic address: jrichard@buffalo.edu.
John P
JP
Richard
Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260-3000, USA.
Tina L
TL
Amyes
Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260-3000, USA.
Bogdana
B
Goryanova
Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260-3000, USA.
Xiang
X
Zhai
D000818:Animals; D055162:Biocatalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D015202:Protein Engineering; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D004798:Enzymes; D011506:Proteins