3WVR
Structure of ATP grasp protein with AMP
Summary for 3WVR
| Entry DOI | 10.2210/pdb3wvr/pdb |
| Related | 3WVQ |
| Descriptor | PGM1, SULFATE ION, ADENOSINE MONOPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | atp grasp domain, ligase, biosynthetic protein |
| Biological source | Streptomyces cirratus |
| Total number of polymer chains | 4 |
| Total formula weight | 197231.36 |
| Authors | Matsui, T.,Noike, M.,Ooya, K.,Sasaki, I.,Hamano, Y.,Maruyama, C.,Ishikawa, J.,Satoh, Y.,Ito, H.,Dairi, T.,Morita, H. (deposition date: 2014-06-04, release date: 2014-11-19, Last modification date: 2024-11-20) |
| Primary citation | Noike, M.,Matsui, T.,Ooya, K.,Sasaki, I.,Ohtaki, S.,Hamano, Y.,Maruyama, C.,Ishikawa, J.,Satoh, Y.,Ito, H.,Morita, H.,Dairi, T. A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin. Nat.Chem.Biol., 11:71-76, 2015 Cited by PubMed Abstract: Peptide antibiotics are typically biosynthesized by one of two distinct machineries in a ribosome-dependent or ribosome-independent manner. Pheganomycin (PGM (1)) and related analogs consist of the nonproteinogenic amino acid (S)-2-(3,5-dihydroxy-4-hydroxymethyl)phenyl-2-guanidinoacetic acid (2) and a proteinogenic core peptide, making their origin uncertain. We report the identification of the biosynthetic gene cluster from Streptomyces cirratus responsible for PGM production. Unexpectedly, the cluster contains a gene encoding multiple precursor peptides along with several genes plausibly encoding enzymes for the synthesis of amino acid 2. We identified PGM1, which has an ATP-grasp domain, as potentially capable of linking the precursor peptides with 2, and validate this hypothesis using deletion mutants and in vitro reconstitution. We document PGM1's substrate permissivity, which could be rationalized by a large binding pocket as confirmed via structural and mutagenesis experiments. This is to our knowledge the first example of cooperative peptide synthesis achieved by ribosomes and peptide ligases using a peptide nucleophile. PubMed: 25402768DOI: 10.1038/nchembio.1697 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.175 Å) |
Structure validation
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