6LTA

Crystal Structure of Nonribosomal peptide synthetases (NRPS), FmoA3 (S1046A)

Summary for 6LTA

• Entry DOI: 10.2210/pdb6lta/pdb
• Descriptor: Nonribosomal peptide synthetase, ACRYLIC ACID (3 entities in total)
• Functional Keywords: nonribosomal peptide synthetases (nrps), jbir-34 and -35, biosynthetic protein
• Biological source: Streptomyces sp. Sp080513GE-23
• Total number of polymer chains: 1
• Total formula weight: 125315.76

Authors

Senda, T.,Harada, A. (deposition date: 2020-01-22, release date: 2021-02-24, Last modification date: 2023-11-29)

Primary citation

Katsuyama, Y.,Sone, K.,Harada, A.,Kawai, S.,Urano, N.,Adachi, N.,Moriya, T.,Kawasaki, M.,Shin-Ya, K.,Senda, T.,Ohnishi, Y.
Structural and Functional Analyses of the Tridomain-Nonribosomal Peptide Synthetase FmoA3 for 4-Methyloxazoline Ring Formation.
Angew.Chem.Int.Ed.Engl., 60:14554-14562, 2021

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 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.

PubMed: 33783097
DOI: 10.1002/anie.202102760

Experimental method

X-RAY DIFFRACTION (2.45 Å)