6po6

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MicroED Structure of a Natural Product VFAThiaGluMicroED Structure of a Natural Product VFAThiaGlu

Structural highlights

6po6 is a 1 chain structure with sequence from Pseudomonas syringae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron crystallography, Resolution 1Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Genome sequencing of environmental bacteria allows identification of biosynthetic gene clusters encoding unusual combinations of enzymes that produce unknown natural products. We identified a pathway in which a ribosomally synthesized small peptide serves as a scaffold for nonribosomal peptide extension and chemical modification. Amino acids are transferred to the carboxyl terminus of the peptide through adenosine triphosphate and amino acyl-tRNA-dependent chemistry that is independent of the ribosome. Oxidative rearrangement, carboxymethylation, and proteolysis of a terminal cysteine yields an amino acid-derived small molecule. Microcrystal electron diffraction demonstrates that the resulting product is isosteric to glutamate. We show that a similar peptide extension is used during the biosynthesis of the ammosamides, which are cytotoxic pyrroloquinoline alkaloids. These results suggest an alternative paradigm for biosynthesis of amino acid-derived natural products.

Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products.,Ting CP, Funk MA, Halaby SL, Zhang Z, Gonen T, van der Donk WA Science. 2019 Jul 19;365(6450):280-284. doi: 10.1126/science.aau6232. PMID:31320540[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Ting CP, Funk MA, Halaby SL, Zhang Z, Gonen T, van der Donk WA. Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products. Science. 2019 Jul 19;365(6450):280-284. doi: 10.1126/science.aau6232. PMID:31320540 doi:http://dx.doi.org/10.1126/science.aau6232

6po6, resolution 1.00Å

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OCA