Substrate-assisted catalysis

Substrate molecules provide catalytic groups in substrate-assisted catalysis... 

Figure 11.16 Substrate-assisted catalysis. Schematic diagram from model building of a substrate, NHa-Phe-Ala-His-Tyr-Gly-COOH (red), bound to the subtilisin mutant His 64-Ala. The diagram illustrates that the His residue of the substrate can occupy roughly the same position in this mutant as His 64 in wild-type subtilisin (see Figure 11.14) and thereby partly restore the catalytic triad.

Carter, P., Wells, J.A. Engineering enzyme specificity by "substrate-assisted catalysis." Science 237 394-399, 1987. 

A structural anomaly in subtilisin has functional consequences Transition-state stabilization in subtilisin is dissected by protein engineering Catalysis occurs without a catalytic triad Substrate molecules provide catalytic groups in substrate-assisted catalysis Conclusion Selected readings... 

SUBSTRATE-ASSISTED CATALYSIS SUBSTRATE CHANNELING Substrate contaminated with the enzyme, BASAL RATE Substrate cycling,... 

Carter, P., Abrahmsen, L. and Wells, J.A. (1991) Probing the mechanism and improving the rate of substrate-assisted catalysis in subtihsin BPN. Biochemistry, 30, 6142-6148. Carter, P. and Wells, J.A. (1988) Dissecting the catalytic triad of a serine protease. 

Schweins,T., Geyer,M., Scheffzek.K., Warshel,A.,mm Kalbitzer.H.R. and Wittinghofer,A. Substrate assisted catalysis as a mechanism for GTP hydrolysis of p2P and other GTP-binding proteins (1995) Struct.Biol. 2, 36-44... 

Further, for antibody catalysis the methyl ester is too small to be an effective epitope but the participation could be induced if an antibody were able to recruit cocaine from the chair conformation to the less stable boat form (see Fig. 4 for the structure) and reorient the syn-protonated amine and benzoyl ester into proximity. Antibodies can provide significant binding energy and in principle antibody binding could effect conformer selection and promotion of substrate-assisted catalysis. To examine this idea, a detailed computational analysis [89] of the energetics of this reaction was also performed for design of novel TSA structures for the alkaline hydrolysis of boat cocaine in comparison with the hydrolysis of chair cocaine. 

Macauley MS, Whitworth GE, Debowski AW, Chin D, Vocadlo DJ. 0-GlcNAcase uses substrate-assisted catalysis kinetic analysis and development of highly selective mechanism-inspired inhibitors. J. Biol. Chem. 2005 280 25313-25322. 

Substrate Positioning and Substrate Assisted Catalysis in the Peptidyl Transferase Center of the Ribosome... 

Kosloff, M., and Selinger, Z. (2001) Substrate assisted catalysis - application to G proteins. Trends Biochem. Sci. 26, 161-6. 

It is straightforward to assume that one of the simple amino acids bound to, and put a handle on, a short RNA. Later on, peptides took over as binding partners of RNAs. The substrate-assisted catalysis used by the ribosome is a prime example for the rate acceleration of peptide bond formation. The 2 -OH of the 3 terminal A residue of the tRNA substrate accelerates the reaction by a factor of 106. Strictly speaking, this scenario corresponds to a combination of two different worlds. 

SCHWEINS, T., Geyer, M., Sgheffzek, K., Warshel, A., Kalbitzer, H. R., WiTTiNGHOFER, A., Substrate-assisted Catalysis as a Mechanism for GTP Hydrolysis of p21 ras and Other GTP-binding Proteins, Nature Struct. Biol. 1995, 2, (1), 36-44. 

Cupp-Vickery, J.R., O. Han, C.R. Hutchinson, andX.L. Poulos (1996). Substrate-assisted catalysis in cytochrome P450eryF. Nat. Struct. Biol. 3, 632-637. 

Ma F, Hanna MA (1999) Biodiesel production a review. Biores Technol 70 1-15 Magnusson A, Hull K, Holmquists M (2001) Creation of an enantioselective hydrolase by engineered substrate-assisted catalysis. J Am Chem Soc 123 4354 355 Manjon A, Iborra JL, Arocas A (1991) Short-chain flavour ester synthesis by immobilized lipase in organic media. Biotechnol Lett 13 339-345 Margolin A (1996) Novel crystalline catalysts. TIBTECH 14 223-230... 

Cupp-Vickery JR, Han O, Hutehinson CR, Poulos TL (1996) Substrate-assisted catalysis in cytochrome P450EryF. Nat Struct Biol 3 632-637... 

Hohnquist et al. have reported a new approach for creating enantioselective hydrolytic en2ymes that they term engineered substrate-assisted catalysis (SAC)... 

A. Jeltsch, J. Alves, H. Wolfes, G. Maass, and A. Pingoud, Proc. Natl. Acad. Sci. (USA), 90, 8499 (1993). Substrate-Assisted Catalysis in the Cleavage of DNA by the EcoRI and EcoRV Restriction Enzymes. 

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