8QNF

Crystal structure of the Condensation domain TomBC from the Tomaymycin non-ribosomal peptide synthetase

Summary for 8QNF

• Entry DOI: 10.2210/pdb8qnf/pdb
• Descriptor: Condensation domain TomBC from the Tomaymycin non-ribosomal peptide synthetase, FORMIC ACID, GLYCEROL, ... (6 entities in total)
• Functional Keywords: non-ribosomal peptide synthetase, tomaymycin, condensation, biosynthetic protein
• Biological source: Streptomyces regensis
• Total number of polymer chains: 1
• Total formula weight: 60220.61

Authors

Karanth, M.,Schmelz, S.,Kirkpatrick, J.,Krausze, J.,Scrima, A.,Carlomagno, T. (deposition date: 2023-09-26, release date: 2024-06-26, Last modification date: 2024-07-03)

Primary citation

Karanth, M.N.,Kirkpatrick, J.P.,Krausze, J.,Schmelz, S.,Scrima, A.,Carlomagno, T.
The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain.
Sci Adv, 10:eadm9404-eadm9404, 2024

PubMed Abstract: In the quest for new bioactive substances, nonribosomal peptide synthetases (NRPS) provide biodiversity by synthesizing nonproteinaceous peptides with high cellular activity. NRPS machinery consists of multiple modules, each catalyzing a unique series of chemical reactions. Incomplete understanding of the biophysical principles orchestrating these reaction arrays limits the exploitation of NRPSs in synthetic biology. Here, we use nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry to solve the conundrum of how intermodular recognition is coupled with loaded carrier protein specificity in the tomaymycin NRPS. We discover an adaptor domain that directly recruits the loaded carrier protein from the initiation module to the elongation module and reveal its mechanism of action. The adaptor domain of the type found here has specificity rules that could potentially be exploited in the design of engineered NRPS machinery.

PubMed: 38896613
DOI: 10.1126/sciadv.adm9404

Experimental method

X-RAY DIFFRACTION (1.65 Å)