8TYI
NMR structure of L5pG ([p23W, G24W]kalata B1)
Summary for 8TYI
| Entry DOI | 10.2210/pdb8tyi/pdb |
| NMR Information | BMRB: 31102 |
| Descriptor | Kalata-B1 (1 entity in total) |
| Functional Keywords | cyclotide, oxidative folding, cystine knot, beta-turn, unknown function |
| Biological source | Oldenlandia affinis |
| Total number of polymer chains | 1 |
| Total formula weight | 2788.19 |
| Authors | Tian, S.,Craik, D.J.,Conan, K.W. (deposition date: 2023-08-25, release date: 2024-03-13, Last modification date: 2024-10-30) |
| Primary citation | Tian, S.,de Veer, S.J.,Durek, T.,Wang, C.K.,Craik, D.J. Nucleation of a key beta-turn promotes cyclotide oxidative folding. J.Biol.Chem., 300:107125-107125, 2024 Cited by PubMed Abstract: Cyclotides are plant-derived peptides characterized by a head-to-tail cyclic backbone and a cystine knot motif comprised of three disulfide bonds. Formation of this motif via in vitro oxidative folding can be challenging and result in misfolded isomers with non-native disulfide connectivities. Here we investigated the effect of β-turn nucleation on cyclotide oxidative folding. Two types of β-turn mimics were grafted into kalata B1 (kB1), individually replacing each of the four β-turns in the folded cyclotide. Insertion of D-Pro-Gly into loop 5 was beneficial to the folding of both cyclic kB1 and a linear form of the peptide. The linear grafted analog folded four-times faster in aqueous conditions than cyclic kB1 in optimized conditions. Additionally, the cyclic analogue folded without the need for redox agents by transitioning through a native-like intermediate that was on-pathway to product formation. Kalata B1 is from the Mobius subfamily of cyclotides. Grafting D-Pro-Gly into loop 5 of cyclotides from two other subfamilies also had a beneficial effect on folding. Our findings demonstrate the importance of a β-turn nucleation site for cyclotide oxidative folding, which could be adopted as a chemical strategy to improve the in vitro folding of diverse cystine-rich peptides. PubMed: 38432638DOI: 10.1016/j.jbc.2024.107125 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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