2N98

Solution structure of acyl carrier protein LipD from Actinoplanes friuliensis

Summary for 2N98

• Entry DOI: 10.2210/pdb2n98/pdb
• NMR Information: BMRB: 25886
• Descriptor: Acyl carrier protein (1 entity in total)
• Functional Keywords: acyl carrier protein, transport protein
• Biological source: Actinoplanes friuliensis
• Total number of polymer chains: 1
• Total formula weight: 9504.63

Authors

Paul, S.,Ishida, H.,Liu, Z.,Nguyen, L.T.,Vogel, H.J. (deposition date: 2015-11-10, release date: 2016-11-16, Last modification date: 2024-05-15)

Primary citation

Paul, S.,Ishida, H.,Nguyen, L.T.,Liu, Z.,Vogel, H.J.
Structural and dynamic characterization of a freestanding acyl carrier protein involved in the biosynthesis of cyclic lipopeptide antibiotics.
Protein Sci., 26:946-959, 2017

PubMed Abstract: Friulimicin is a cyclic lipodecapeptide antibiotic that is produced by Actinoplanes friuliensis. Similar to the related lipopeptide drug daptomycin, the peptide skeleton of friulimicin is synthesized by a large multienzyme nonribosomal peptide synthetase (NRPS) system. The LipD protein plays a major role in the acylation reaction of friulimicin. The attachment of the fatty acid group promotes its antibiotic activity. Phylogenetic analysis reveals that LipD is most closely related to other freestanding acyl carrier proteins (ACPs), for which the genes are located near to NRPS gene clusters. Here, we report that the solution NMR structure of apo-LipD is very similar to other four-helix bundle forming ACPs from fatty acid synthase (FAS), polyketide synthase, and NRPS systems. By recording NMR dynamics data, we found that the backbone motions in holo-LipD are more restricted than in apo-LipD due to the attachment of phosphopantetheine moiety. This enhanced stability of holo-LipD was also observed in differential scanning calorimetry experiments. Furthermore, we demonstrate that, unlike several other ACPs, the folding of LipD does not depend on the presence of divalent cations, although the presence of Mg or Ca can increase the protein stability. We propose that small structural rearrangements in the tertiary structure of holo-LipD which lead to the enhanced stability are important for the cognate enzyme recognition for the acylation reaction. Our results also highlight the different surface charges of LipD and FAS-ACP from A. friuliensis that would allow the acyl-CoA ligase to interact preferentially with the LipD instead of binding to the FAS-ACP.

PubMed: 28187530
DOI: 10.1002/pro.3138

Experimental method

SOLUTION NMR