5DU9
First condensation domain of the calcium-dependent antibiotic synthetase in complex with substrate analogue 2a
Summary for 5DU9
| Entry DOI | 10.2210/pdb5du9/pdb |
| Related | 5DUA |
| Descriptor | CDA peptide synthetase I, SULFATE ION, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | nonribosomal peptide synthetase, condensation domain, chemical probe, substrate analogue, phosphopantetheine binding protein |
| Biological source | Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145) |
| Total number of polymer chains | 2 |
| Total formula weight | 97472.40 |
| Authors | Bloudoff, K.,Alonzo, D.A.,Schmeing, T.M. (deposition date: 2015-09-18, release date: 2016-03-30, Last modification date: 2024-11-06) |
| Primary citation | Bloudoff, K.,Alonzo, D.A.,Schmeing, T.M. Chemical Probes Allow Structural Insight into the Condensation Reaction of Nonribosomal Peptide Synthetases. Cell Chem Biol, 23:331-339, 2016 Cited by PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) synthesize a vast variety of small molecules, including antibiotics, antitumors, and immunosuppressants. The NRPS condensation (C) domain catalyzes amide bond formation, the central chemical step in nonribosomal peptide synthesis. The catalytic mechanism and substrate determinants of the reaction are under debate. We developed chemical probes to structurally study the NRPS condensation reaction. These substrate analogs become covalently tethered to a cysteine introduced near the active site, to mimic covalent substrate delivery by carrier domains. They are competent substrates in the condensation reaction and behave similarly to native substrates. Co-crystal structures show C domain-substrate interactions, and suggest that the catalytic histidine's principle role is to position the α-amino group for nucleophilic attack. Structural insight provided by these co-complexes also allowed us to alter the substrate specificity profile of the reaction with a single point mutation. PubMed: 26991102DOI: 10.1016/j.chembiol.2016.02.012 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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