7B2B

Solution structure of a non-covalent extended docking domain complex of the Pax NRPS: PaxA T1-CDD/PaxB NDD

Summary for 7B2B

• Entry DOI: 10.2210/pdb7b2b/pdb
• NMR Information: BMRB: 34575
• Descriptor: Amino acid adenylation domain-containing protein, Peptide synthetase PaxA (2 entities in total)
• Functional Keywords: protein, protein binding
• Biological source: Xenorhabdus cabanillasii; More
• Total number of polymer chains: 2
• Total formula weight: 15592.59

Authors

Watzel, J.,Sarawi, S.,Duchardt-Ferner, E.,Bode, H.B.,Woehnert, J. (deposition date: 2020-11-26, release date: 2021-06-16, Last modification date: 2024-07-03)

Primary citation

Watzel, J.,Duchardt-Ferner, E.,Sarawi, S.,Bode, H.B.,Wohnert, J.
Cooperation between a T Domain and a Minimal C-Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS.
Angew.Chem.Int.Ed.Engl., 60:14171-14178, 2021

PubMed Abstract: Non-ribosomal peptide synthetases (NRPS) produce natural products from amino acid building blocks. They often consist of multiple polypeptide chains which assemble in a specific linear order via specialized N- and C-terminal docking domains ( DDs). Typically, docking domains function independently from other domains in NRPS assembly. Thus, docking domain replacements enable the assembly of "designer" NRPS from proteins that normally do not interact. The multiprotein "peptide-antimicrobial-Xenorhabdus" (PAX) peptide-producing PaxS NRPS is assembled from the three proteins PaxA, PaxB and PaxC. Herein, we show that the small DD of PaxA cooperates with its preceding thiolation (T ) domain to bind the DD of PaxB with very high affinity, establishing a structural and thermodynamical basis for this unprecedented docking interaction, and we test its functional importance in vivo in a truncated PaxS assembly line. Similar docking interactions are apparently present in other NRPS systems.

PubMed: 33876501
DOI: 10.1002/anie.202103498

Experimental method

SOLUTION NMR