7rfa | pdb_00007rfa

NMR Solution structure of linear [T20K]kalataB1

spinqualitylabelsall models 7rfa Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rfa is a 1 chain structure with sequence from Oldenlandia affinis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KAB4_OLDAF Probably participates in a plant defense mechanism. Publication Abstract from PubMed The cyclotide T20K inhibits the proliferation of human immune cells and is currently in clinical trials for multiple sclerosis. Here, we provide novel functional data and mechanistic insights into structure-activity relationships of T20K. Analogs with partial or complete reduction of the cystine knot had loss of function in proliferation experiments. Similarly, an acyclic analog of T20K was inactive in lymphocyte bioassays. The lack of activity of non-native peptide analogs appears to be associated with the ability of cyclotides to interact with and penetrate cell membranes, since cellular uptake studies demonstrated fast fractional transfer only of the native peptide into the cytosol of human immune cells. Therefore, structural differences between cyclic and linear native folded peptides were investigated by NMR to elucidate structure-activity relationships. Acyclic T20K had a less rigid backbone and considerable structural changes in loops 1 and 6 compared to the native cyclic T20K, supporting the idea that the cyclic cystine knot motif is a unique bioactive scaffold. This study provides evidence that this structural motif in cyclotides governs bioactivity, interactions with and transport across biological membranes, and the structural integrity of these peptides. These observations could be useful to understand the structure-activity of other cystine knot proteins due to the structural conservation of the cystine knot motif across evolution and to provide guidance for the design of novel cyclic cysteine-stabilized molecules. Importance of the Cyclic Cystine Knot Structural Motif for Immunosuppressive Effects of Cyclotides.,Hellinger R, Muratspahic E, Devi S, Koehbach J, Vasileva M, Harvey PJ, Craik DJ, Grundemann C, Gruber CW ACS Chem Biol. 2021 Sep 30. doi: 10.1021/acschembio.1c00524. PMID:34592097 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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