Structure and Cooperativity in Substrate–Enzyme Interactions: Perspectives on Enzyme Engineering and Inhibitor Design

Rajakumara, Eerappa and Abhishek, Suman and Nitin, Kulhar and et al, . (2022) Structure and Cooperativity in Substrate–Enzyme Interactions: Perspectives on Enzyme Engineering and Inhibitor Design. ACS Chemical Biology, 17 (2). pp. 266-280. ISSN 1554-8929

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Abstract

Enzyme-based synthetic chemistry provides a green way to synthesize industrially important chemical scaffolds and provides incomparable substrate specificity and unmatched stereo-, regio-, and chemoselective product formation. However, using biocatalysts at an industrial scale has its challenges, like their narrow substrate scope, limited stability in large-scale one-pot reactions, and low expression levels. These limitations can be overcome by engineering and fine-tuning these biocatalysts using advanced protein engineering methods. A detailed understanding of the enzyme structure and catalytic mechanism and its structure-function relationship, cooperativity in binding of substrates, and dynamics of substrate-enzyme-cofactor complexes is essential for rational enzyme engineering for a specific purpose. This Review covers all these aspects along with an in-depth categorization of various industrially and pharmaceutically crucial bisubstrate enzymes based on their reaction mechanisms and their active site and substrate/cofactor-binding site structures. As the bisubstrate enzymes constitute around 60% of the known industrially important enzymes, studying their mechanism of actions and structure-activity relationship gives significant insight into deciding the targets for protein engineering for developing industrial biocatalysts. Thus, this Review is focused on providing a comprehensive knowledge of the bisubstrate enzymes’ structure, their mechanisms, and protein engineering approaches to develop them into industrial biocatalysts. © 2022 American Chemical Society

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IITH Creators:

IITH Creators	ORCiD
Rajakumara, Eerappa	https://orcid.org/0000-0002-9341-0070

Item Type:

Article

Additional Information:

E.R. thanks the Department of Biotechnology (DBT) and the Science and Engineering Research Board, Department of Science and Technology, Government of India, for the Ramalingaswami re-entry fellowship and the Early Career Research Award, respectively. S.A. and K.N. thank the Ministry of Human Resource Development, Government of India, for the fellowship. D.S. thanks the Council of Scientific and Industrial Research, Government of India for the fellowship. M.D.D. is supported through funds from IPB Halle.

Uncontrolled Keywords:

Biocatalysis; Catalysis; Catalytic Domain; Enzymes; Protein Engineering; Substrate Specificity

Subjects:

Others > Biochemistry
Others > Biotechnology
Materials Engineering > Materials engineering

Divisions:

Department of Biotechnology
Department of Material Science Engineering

Depositing User:

. LibTrainee 2021

Date Deposited:

18 Jul 2022 11:06

Last Modified:

18 Jul 2022 11:06