title: The crystal structure of BlmI as a model for  nonribosomal peptide synthetase peptidyl  carrier proteins.
abstract: Carrier proteins (CPs) play a critical role in the biosynthesis of various natural products, especially in nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymology, where the CPs are referred to as peptidyl-carrier proteins (PCPs) or acyl-carrier proteins (ACPs), respectively. CPs can either be a domain in large multifunctional polypeptides or standalone proteins, termed Type I and Type II, respectively. There have been many biochemical studies of the Type I PKS and NRPS CPs, and of Type II ACPs. However, recently a number of Type II PCPs have been found and biochemically characterized. In order to understand the possible interaction surfaces for combinatorial biosynthetic efforts we crystallized the first characterized and representative Type II PCP member, BlmI, from the bleomycin biosynthetic pathway from Streptomyces verticillus ATCC 15003. The structure is similar to CPs in general but most closely resembles PCPs. Comparisons with previously determined PCP structures in complex with catalytic domains reveals a common interaction surface. This surface is highly variable in charge and shape, which likely confers specificity for interactions. Previous nuclear magnetic resonance (NMR) analysis of a prototypical Type I PCP excised from the multimodular context revealed three conformational states. Comparison of the states with the structure of BlmI and other PCPs reveals that only one of the NMR states is found in other studies, suggesting the other two states may not be relevant. The state represented by the BlmI crystal structure can therefore serve as a model for both Type I and Type II PCPs.
authors: Jeremy R
authors: JR
authors: Lohman
authors: Ming
authors: M
authors: Ma
authors: Marianne E
authors: ME
authors: Cuff
authors: Lance
authors: L
authors: Bigelow
authors: Jessica
authors: J
authors: Bearden
authors: Gyorgy
authors: G
authors: Babnigg
authors: Andrzej
authors: A
authors: Joachimiak
authors: George N
authors: GN
authors: Phillips
authors: Ben
authors: B
authors: Shen
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D019295:Computational Biology; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C121823:peptidyl carrier protein, type II, Streptomyces verticillus