6ava

Exploring Cystine Dense Peptide Space to Open a Unique Molecular Toolbox

spinqualitylabelsall models 6ava, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ava is a 2 chain structure with sequence from Mesobuthus eupeus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CTXI1_MESEU Toxin with unknown function in healthy organisms. On glioma cells, interacts with chloride channels (probably ClC-3/CLCN3) and MMP2 at the surface of glioma cells. This complex is then internalized via caveolae, thus inhibiting the chloride channels necessary for cell shrinkage and tumor propagation (By similarity). Publication Abstract from PubMed Peptides folded through interwoven disulfides display extreme biochemical properties and unique medicinal potential. However, their exploitation has been hampered by the limited amounts isolatable from natural sources and the expense of chemical synthesis. We developed reliable biological methods for high-throughput expression, screening and large-scale production of these peptides: 46 were successfully produced in multimilligram quantities, and >600 more were deemed expressible through stringent screening criteria. Many showed extreme resistance to temperature, proteolysis and/or reduction, and all displayed inhibitory activity against at least 1 of 20 ion channels tested, thus confirming their biological functionality. Crystal structures of 12 confirmed proper cystine topology and the utility of crystallography to study these molecules but also highlighted the need for rational classification. Previous categorization attempts have focused on limited subsets featuring distinct motifs. Here we present a global definition, classification and analysis of >700 structures of cystine-dense peptides, providing a unifying framework for these molecules. Screening, large-scale production and structure-based classification of cystine-dense peptides.,Correnti CE, Gewe MM, Mehlin C, Bandaranayake AD, Johnsen WA, Rupert PB, Brusniak MY, Clarke M, Burke SE, De Van Der Schueren W, Pilat K, Turnbaugh SM, May D, Watson A, Chan MK, Bahl CD, Olson JM, Strong RK Nat Struct Mol Biol. 2018 Mar;25(3):270-278. doi: 10.1038/s41594-018-0033-9. Epub, 2018 Feb 26. PMID:29483648 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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