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Structural Biology of Nonribosomal Peptide Synthetases

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Book cover Nonribosomal Peptide and Polyketide Biosynthesis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1401))

Abstract

The nonribosomal peptide synthetases are modular enzymes that catalyze synthesis of important peptide products from a variety of standard and non-proteinogenic amino acid substrates. Within a single module are multiple catalytic domains that are responsible for incorporation of a single residue. After the amino acid is activated and covalently attached to an integrated carrier protein domain, the substrates and intermediates are delivered to neighboring catalytic domains for peptide bond formation or, in some modules, chemical modification. In the final module, the peptide is delivered to a terminal thioesterase domain that catalyzes release of the peptide product. This multi-domain modular architecture raises questions about the structural features that enable this assembly line synthesis in an efficient manner. The structures of the core component domains have been determined and demonstrate insights into the catalytic activity. More recently, multi-domain structures have been determined and are providing clues to the features of these enzyme systems that govern the functional interaction between multiple domains. This chapter describes the structures of NRPS proteins and the strategies that are being used to assist structural studies of these dynamic proteins, including careful consideration of domain boundaries for generation of truncated proteins and the use of mechanism-based inhibitors that trap interactions between the catalytic and carrier protein domains.

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Acknowledgments

The research from our lab that is included in this review has been supported by the National Institutes of Health (GM-068440).

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Authors and Affiliations

  1. Hauptman-Woodward Medical Research Institute, 700 Ellicott St, Buffalo, NY, 14203-1102, USA

    Bradley R. Miller & Andrew M. Gulick

  2. Department of Structural Biology, University at Buffalo, Buffalo, NY, USA

    Bradley R. Miller & Andrew M. Gulick

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  1. Bradley R. Miller
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  2. Andrew M. Gulick
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Correspondence to Andrew M. Gulick .

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Editors and Affiliations

  1. Donald Danforth Plant Science Center, Saint Louis, Missouri, USA

    Bradley S. Evans

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Miller, B.R., Gulick, A.M. (2016). Structural Biology of Nonribosomal Peptide Synthetases. In: Evans, B. (eds) Nonribosomal Peptide and Polyketide Biosynthesis. Methods in Molecular Biology, vol 1401. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3375-4_1

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  • DOI: https://doi.org/10.1007/978-1-4939-3375-4_1

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