6ATN
Exploring Cystine Dense Peptide Space to Open a Unique Molecular Toolbox
Summary for 6ATN
| Entry DOI | 10.2210/pdb6atn/pdb |
| Related | 6ATL 6ATM |
| Descriptor | Potassium channel toxin alpha-KTx 4.5 (2 entities in total) |
| Functional Keywords | knottins, cystine knot, toxins, toxin |
| Biological source | Tityus costatus (Brazilian scorpion) |
| Cellular location | Secreted: Q5G8B6 |
| Total number of polymer chains | 1 |
| Total formula weight | 4144.03 |
| Authors | Gewe, M.M.,Rupert, P.,Strong, R.K. (deposition date: 2017-08-29, release date: 2018-02-28, Last modification date: 2018-03-14) |
| Primary citation | Correnti, C.E.,Gewe, M.M.,Mehlin, C.,Bandaranayake, A.D.,Johnsen, W.A.,Rupert, P.B.,Brusniak, M.Y.,Clarke, M.,Burke, S.E.,De Van Der Schueren, W.,Pilat, K.,Turnbaugh, S.M.,May, D.,Watson, A.,Chan, M.K.,Bahl, C.D.,Olson, J.M.,Strong, R.K. Screening, large-scale production and structure-based classification of cystine-dense peptides. Nat. Struct. Mol. Biol., 25:270-278, 2018 Cited by PubMed Abstract: 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. PubMed: 29483648DOI: 10.1038/s41594-018-0033-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.76 Å) |
Structure validation
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