Format

Send to

Choose Destination
Methods Mol Biol. 2016;1401:3-29. doi: 10.1007/978-1-4939-3375-4_1.

Structural Biology of Nonribosomal Peptide Synthetases.

Author information

1
Hauptman-Woodward Medical Research Institute, 700 Ellicott St, Buffalo, NY, 14203-1102, USA.
2
Department of Structural Biology, University at Buffalo, Buffalo, NY, USA.
3
Hauptman-Woodward Medical Research Institute, 700 Ellicott St, Buffalo, NY, 14203-1102, USA. gulick@hwi.buffalo.edu.
4
Department of Structural Biology, University at Buffalo, Buffalo, NY, USA. gulick@hwi.buffalo.edu.

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.

KEYWORDS:

Enzymology; Metabolic pathways; Modular enzymes; Nonribosomal peptide synthetase; Peptides; Siderophores; Structural biology

PMID:
26831698
PMCID:
PMC4760355
DOI:
10.1007/978-1-4939-3375-4_1
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center