Structural Biology of Nonribosomal Peptide Synthetases
| Autor: | Bradley R. Miller, Andrew M. Gulick |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Stereochemistry Protein Conformation Peptide Biology Bioinformatics Crystallography X-Ray Article 03 medical and health sciences Residue (chemistry) Thioesterase Nonribosomal peptide Catalytic Domain Peptide bond Animals Humans Peptide Synthases Nuclear Magnetic Resonance Biomolecular chemistry.chemical_classification 030102 biochemistry & molecular biology Bacteria Amino acid Protein Structure Tertiary 030104 developmental biology Enzyme chemistry Structural biology Crystallization |
| Zdroj: | Methods in Molecular Biology ISBN: 9781493933730 |
| ISSN: | 1940-6029 |
| Popis: | The non-ribosomal 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. |
| Databáze: | OpenAIRE |
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