biostudies-literatureBloudoff KCanada Research Chair in Macromolecular MachinesHuman Frontiers Science ProgramCanadian Institutes of Health ResearchCIHR3137-50https://www.ebi.ac.uk/biostudies/studies/S-EPMC4318696biostudies-literatureUnknown425(17)Nonribosomal peptide synthetases (NRPSs) are large modular macromolecular machines that produce small peptide molecules with wide-ranging biological activities, such as antibiotics and green chemicals. The condensation (C) domain is responsible for amide bond formation, the central chemical step in nonribosomal peptide synthesis. Here we present two crystal structures of the first condensation domain of the calcium-dependent antibiotic (CDA) synthetase (CDA-C1) from Streptomyces coelicolor, determined at resolutions 1.8Å and 2.4Å. The conformations adopted by CDA-C1 are quite similar in these two structures yet distinct from those seen in other NRPS C domain structures. HPLC-based reaction assays show that this CDA-C1 construct is catalytically active, and small-angle X-ray scattering expeJournal of molecular biologyCrystal structures of the first condensation domain of CDA synthetase suggest conformational changes during the synthetic cycle of nonribosomal peptide synthetases.PMC4318696MOP 106615106615-2106615-1Bloudoff KRodionov DSchmeing TMfalseCrystal structures of the first condensation domain of CDA synthetase suggest conformational changes during the synthetic cycle of nonribosomal peptide synthetases.Nonribosomal peptide synthetases (NRPSs) are large modular macromolecular machines that produce small peptide molecules with wide-ranging biological activities, such as antibiotics and green chemicals. The condensation (C) domain is responsible for amide bond formation, the central chemical step in nonribosomal peptide synthesis. Here we present two crystal structures of the first condensation domain of the calcium-dependent antibiotic (CDA) synthetase (CDA-C1) from Streptomyces coelicolor, determined at resolutions 1.8Å and 2.4Å. The conformations adopted by CDA-C1 are quite similar in these two structures yet distinct from those seen in other NRPS C domain structures. HPLC-based reaction assays show that this CDA-C1 construct is catalytically active, and small-angle X-ray scattering expe2013-01-01T00:00:00Z2013 Sep2026-05-03T05:40:06.346Z2026-04-07T18:53:54.442ZS-EPMC43186962375615910.1016/j.jmb.2013.06.003