+Search query
-Structure paper
Title | Structural and Functional Analyses of the Tridomain-Nonribosomal Peptide Synthetase FmoA3 for 4-Methyloxazoline Ring Formation. |
---|---|
Journal, issue, pages | Angew Chem Int Ed Engl, Vol. 60, Issue 26, Page 14554-14562, Year 2021 |
Publish date | Jun 21, 2021 |
Authors | Yohei Katsuyama / Kaoru Sone / Ayaka Harada / Seiji Kawai / Naoki Urano / Naruhiko Adachi / Toshio Moriya / Masato Kawasaki / Kazuo Shin-Ya / Toshiya Senda / Yasuo Ohnishi / |
PubMed Abstract | Nonribosomal peptide synthetases (NRPSs) are attractive targets for bioengineering to generate useful peptides. FmoA3 is a single modular NRPS composed of heterocyclization (Cy), adenylation (A), and ...Nonribosomal peptide synthetases (NRPSs) are attractive targets for bioengineering to generate useful peptides. FmoA3 is a single modular NRPS composed of heterocyclization (Cy), adenylation (A), and peptidyl carrier protein (PCP) domains. It uses 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 activity. The collective data support a proposed catalytic cycle of FmoA3. |
External links | Angew Chem Int Ed Engl / PubMed:33783097 |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.45 - 4.1 Å |
Structure data | EMDB-30440: PDB-6lta: PDB-6ltb: PDB-6ltc: PDB-6ltd: |
Chemicals | ChemComp-AKR: ChemComp-HOH: ChemComp-ANP: ChemComp-AMP: ChemComp-EW6: ChemComp-SO4: ChemComp-CL: |
Source |
|
Keywords | BIOSYNTHETIC PROTEIN / Nonribosomal peptide synthetases (NRPS) / JBIR-34 and -35 |