6OZV

The structure of condensation and adenylation domains of teixobactin-producing nonribosomal peptide synthetase Txo1 serine module in complex with AMP

Summary for 6OZV

• Entry DOI: 10.2210/pdb6ozv/pdb
• Related: 6OYF
• Descriptor: Txo1, ADENOSINE MONOPHOSPHATE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: nonribosomal peptide synthetase, teixobactin, txo1, condensation domain, adenylation domain, structural genomics, center for structural genomics of infectious diseases, csgid, biosynthetic protein
• Biological source: Eleftheria terrae
• Total number of polymer chains: 1
• Total formula weight: 97389.40

Authors

Tan, K.,Zhou, M.,Jedrzejczak, R.,Babnigg, G.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2019-05-16, release date: 2019-05-29, Last modification date: 2026-03-25)

Primary citation

Tan, K.,Zhou, M.,Jedrzejczak, R.P.,Wu, R.,Higuera, R.A.,Borek, D.,Babnigg, G.,Joachimiak, A.
Structures of teixobactin-producing nonribosomal peptide synthetase condensation and adenylation domains.
Curr Res Struct Biol, 2:14-24, 2020

PubMed Abstract: The recently discovered antibiotic teixobactin is produced by uncultured soil bacteria. The antibiotic inhibits cell wall synthesis of Gram-positive bacteria by binding to precursors of cell wall building blocks, and therefore it is thought to be less vulnerable to development of resistance. Teixobactin is synthesized by two nonribosomal peptide synthetases (NRPSs), encoded by and genes. Like other NRPSs, the Txo1 and Txo2 synthetases are large, multifunctional, and comprised of several modules. Each module is responsible for catalysis of a distinct step of teixobactin synthesis and contains specific functional units, commonly including a condensation (C) domain, an adenylation (A) domain, and a peptidyl carrier protein (PCP) domain. Here we report the structures of the C-A bidomains of the two L-Ser condensing modules, from Txo1 and Txo2, respectively. In the structure of the C domain of the L-Ser subunit of Txo1, a large conformational change is observed, featuring an outward swing of its N-terminal α-helix. This repositioning, if functionally validated, provides the necessary conformational change for the condensation reaction in C domain, and likely represents a regulatory mechanism. In an A subdomain, a well-coordinated Mg cation is observed, which is required in the adenylation reaction. The Mg-binding site is defined by a largely conserved amino acid sequence motif and is coordinated by the α-phosphate group of AMP (or ATP) when present, providing some structural evidence for the role of the metal cation in the catalysis of A domain.

PubMed: 34235466
DOI: 10.1016/j.crstbi.2020.01.002

Experimental method

X-RAY DIFFRACTION (2.18 Å)