Substrate assisted catalysis - Application to G proteins

Mickey Kosloff; Zvi Selinger

doi:10.1016/S0968-0004(00)01748-5

Substrate assisted catalysis - Application to G proteins

Research output: Contribution to journal › Review article › peer-review

Abstract

The idea that both the substrate and the enzyme contribute to catalysis (substrate assisted catalysis; SAC) is applicable to guanine nucleotide-binding proteins (G proteins). Naturally occurring SAC uses GTP as a general base in the GTPase reaction catalyzed by G proteins. Engineered SAC has identified a putative rate-limiting step for the GTPase reaction and shown that GTPase-deficient oncogenic Ras mutants are not irreversibly impaired. Thus, anti-cancer drugs could potentially be designed to restore the blocked GTPase reaction.

Original language	English
Pages (from-to)	161-166
Number of pages	6
Journal	Trends in Biochemical Sciences
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/S0968-0004(00)01748-5
State	Published - 1 Mar 2001
Externally published	Yes

Bibliographical note

Funding Information:
We thank R. Kornberg for stimulating discussion, and M. Schramm and D. Cassel for helpful comments. Our research was supported by grants from the Israeli Science Foundation (ISF), the National Institute of Health (EY 03529) and the Minerva Foundation.

ASJC Scopus subject areas

Biochemistry
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0968-0004(00)01748-5

Cite this

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abstract = "The idea that both the substrate and the enzyme contribute to catalysis (substrate assisted catalysis; SAC) is applicable to guanine nucleotide-binding proteins (G proteins). Naturally occurring SAC uses GTP as a general base in the GTPase reaction catalyzed by G proteins. Engineered SAC has identified a putative rate-limiting step for the GTPase reaction and shown that GTPase-deficient oncogenic Ras mutants are not irreversibly impaired. Thus, anti-cancer drugs could potentially be designed to restore the blocked GTPase reaction.",

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AU - Selinger, Zvi

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N2 - The idea that both the substrate and the enzyme contribute to catalysis (substrate assisted catalysis; SAC) is applicable to guanine nucleotide-binding proteins (G proteins). Naturally occurring SAC uses GTP as a general base in the GTPase reaction catalyzed by G proteins. Engineered SAC has identified a putative rate-limiting step for the GTPase reaction and shown that GTPase-deficient oncogenic Ras mutants are not irreversibly impaired. Thus, anti-cancer drugs could potentially be designed to restore the blocked GTPase reaction.

AB - The idea that both the substrate and the enzyme contribute to catalysis (substrate assisted catalysis; SAC) is applicable to guanine nucleotide-binding proteins (G proteins). Naturally occurring SAC uses GTP as a general base in the GTPase reaction catalyzed by G proteins. Engineered SAC has identified a putative rate-limiting step for the GTPase reaction and shown that GTPase-deficient oncogenic Ras mutants are not irreversibly impaired. Thus, anti-cancer drugs could potentially be designed to restore the blocked GTPase reaction.

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JF - Trends in Biochemical Sciences

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Substrate assisted catalysis - Application to G proteins

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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