6ATU

Exploring Cystine Dense Peptide Space to Open a Unique Molecular Toolbox

6ATU の概要

• エントリーDOI: 10.2210/pdb6atu/pdb
• 関連するPDBエントリー: 6ATL 6ATM 6ATN 6ATS
• 分子名称: Elafin (2 entities in total)
• 機能のキーワード: knottins, cystine knot, toxins, toxin
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted: P19957
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 110850.37

構造登録者

Gewe, M.M.,Rupert, P.,Strong, R.K. (登録日: 2017-08-29, 公開日: 2018-02-28, 最終更新日: 2024-10-23)

主引用文献

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

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: 29483648
DOI: 10.1038/s41594-018-0033-9

実験手法

X-RAY DIFFRACTION (2.4 Å)