title: New Structural Data Reveal the Motion of Carrier Proteins in Nonribosomal Peptide Synthesis.
abstract: The nonribosomal peptide synthetases (NRPSs) are one of the most promising resources for the production of new bioactive molecules. The mechanism of NRPS catalysis is based around sequential catalytic domains: these are organized into modules, where each module selects, modifies, and incorporates an amino acid into the growing peptide. The intermediates formed during NRPS catalysis are delivered between enzyme centers by peptidyl carrier protein (PCP) domains, which makes PCP interactions and movements crucial to NRPS mechanism. PCP movement has been linked to the domain alternation cycle of adenylation (A) domains, and recent complete NRPS module structures provide support for this hypothesis. However, it appears as though the A domain alternation alone is insufficient to account for the complete NRPS catalytic cycle and that the loaded state of the PCP must also play a role in choreographing catalysis in these complex and fascinating molecular machines.
authors.affiliation: Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120, Heidelberg, Germany.
authors.forename: Tiia
authors.initials: T
authors.lastname: Kittilä
authors.affiliation: Department of Chemistry, Haverford College, Haverford, PA, 19041, USA.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Mollo
authors.affiliation: Department of Chemistry, Haverford College, Haverford, PA, 19041, USA. lcharkou@haverford.edu.
authors.forename: Louise K
authors.initials: LK
authors.lastname: Charkoudian
authors.affiliation: Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120, Heidelberg, Germany. max.cryle@monash.edu.|EMBL Australia, Monash University, Clayton, Victoria, 3800, Australia. max.cryle@monash.edu.|The Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, 3800, Australia. max.cryle@monash.edu.
authors.forename: Max J
authors.identifier: 0000-0002-9739-6157
authors.initials: MJ
authors.lastname: Cryle
mesh_terms: D055162:Biocatalysis; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D002352:Carrier Proteins; D010455:Peptides; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase
keywords: biosynthesis; enzymes; nonribosomal peptide synthetases; peptidyl carrier protein; protein structures