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Structural and Functional Analyses of the Tridomain‐Nonribosomal Peptide Synthetase FmoA3 for 4‐Methyloxazoline Ring Formation
- Source :
- Angewandte Chemie International Edition. 60:14554-14562
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Nonribosomal peptide synthetases (NRPSs) are attractive targets for bioengineering to generate useful peptides . F moA3 is a single modular NRPS composed of heterocyclization (Cy), adenylation (A), and peptidyl carrier protein (PCP) domains. It use s α - methyl- l -serine to synthesize a 4-methyloxazoline ring, probably with another Cy domain in the preceding module FmoA2. Here, we determined the head-to-tail homodimeric structures of FmoA3 by X-ray crystallography ( apo -form, with adenylyl-imidodiphosphate and α -methyl- l -seryl-AMP) and cryogenic electron microscopy single particle analysis, and performed site-directed mutagenesis experiments. The data revealed that α -methyl- l -serine can be accommodated in the active site because of the extra space around Ala688. The Cy domains of FmoA2 and FmoA3 catalyze peptide bond formation and heterocyclization, respectively. FmoA3's Cy domain seems to lose its donor PCP binding activit y. The collective data support a proposed catalytic cycle of FmoA3.
- Subjects :
- Models, Molecular
chemistry.chemical_classification
biology
Stereochemistry
Cryoelectron Microscopy
Mutagenesis
Active site
General Medicine
General Chemistry
Crystallography, X-Ray
Ring (chemistry)
Catalysis
Serine
chemistry
Catalytic cycle
Nonribosomal peptide
biology.protein
Peptide bond
Peptide Synthases
Oxazoles
Adenylylation
Subjects
Details
- ISSN :
- 15213773 and 14337851
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie International Edition
- Accession number :
- edsair.doi.dedup.....6baf66acaacf62d25832f6872199d2f2
- Full Text :
- https://doi.org/10.1002/anie.202102760