Knots in Proteins

Liang, Chengzhi; Mislow, Kurt

doi:10.1021/ja00103a057

Cited by 111 publications

(51 citation statements)

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“…Links have been found in DNA (9,10) and have been synthesized in template synthesis (11,12). In proteins, the first attempts to identify links were made by Mislow (13,14). In his approach, however, the link-forming loops were defined either by including interaction with a metal ion (noncovalent loop) or by at least two disulfide bonds for each (covalent) loop.…”

mentioning

confidence: 99%

Topological knots and links in proteins

Dąbrowski-Tumański

Sułkowska

2017

Proc. Natl. Acad. Sci. U.S.A.

118

100

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Twenty years after their discovery, knots in proteins are now quite well understood. They are believed to be functionally advantageous and provide extra stability to protein chains. In this work, we go one step further and search for links-entangled structures, more complex than knots, which consist of several components. We derive conditions that proteins need to meet to be able to form links. We search through the entire Protein Data Bank and identify several sequentially nonhomologous chains that form a Hopf link and a Solomon link. We relate topological properties of these proteins to their function and stability and show that the link topology is characteristic of eukaryotes only. We also explain how the presence of links affects the folding pathways of proteins. Finally, we define necessary conditions to form Borromean rings in proteins and show that no structure in the Protein Data Bank forms a link of this type.folding | catenanes | slipknot | lasso | disulphide bridge K notted proteins have been identified in all kingdoms of life, in organisms separated even by 1 billion years of evolution (1-5). High conservation (5) of knotted motifs and their location (usually) in enzymatic active sites indicates that knots are crucial for protein function. Over 1,300 knotted or slipknotted (shoelace-type) structures, including the trefoil (31), figure-eight (41), three-twist (52), and Stevedore's (61) knots (4, 6, 7), have been deposited in the Protein Data Bank (PDB) to date according to KnotProt (8).Mathematically, a knot is defined as an embedding of a circle into a 3D space. A link is a generalization of a knot, defined as an embedding of a finite set of circles. The simplest examples of links are, e.g., the Hopf link and the Solomon link ( Fig. 1, Center). Links have been found in DNA (9, 10) and have been synthesized in template synthesis (11,12). In proteins, the first attempts to identify links were made by Mislow (13,14). In his approach, however, the link-forming loops were defined either by including interaction with a metal ion (noncovalent loop) or by at least two disulfide bonds for each (covalent) loop. The links formed by covalent loops, each closed by one disulfide bridge only, were considered "unlikely to lead to knots or links" (ref. 14, p. 4,202) by Mislow and therefore hardly examined. Moreover, all of the structures were scanned only by "visual examination of their 3D structures" (ref. 14, p. 4,202). To date, the only known simple protein links are designed p53 protein catenanes (15) (with the backbones of both chains artificially closed, forming linked loops) and a thermophilic two-chain complex (16) (with linked loops formed by the backbones closed via disulfide bridges). However, the discovery of a wide class of complex lasso proteins (17, 18), in which a chain pierces a covalently closed loop (Fig. 1), opens a unique possibility of defining and identifying links. Such links (or more formally, pretzelanes) are defined using covalent loops closed by disulfide bridges in a single-protein cha...

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confidence: 99%

Topological knots and links in proteins

Dąbrowski-Tumański

Sułkowska

2017

Proc. Natl. Acad. Sci. U.S.A.

118

100

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“…Liang and Mislow examined X-ray structures of many proteins and, to the surprise of many molecular chemists and biochemists, they found catenanes and even trefoil knots [9,10]. This remarkable finding addresses the general question of whether the topological properties of proteins have any biological significance.…”

Section: Biological Topology: Dna and Proteinsmentioning

confidence: 93%

“…In 1994, Liang and Mislow presented fascinating discussions on knots and links in relation to chirality [9][10]. This breakthrough work should help bridge the gap between the communities of mathematical topologists and molecular chemists.…”

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confidence: 99%

Molecular Knots

Dietrich‐Buchecker

Colasson

Sauvage

2005

Topics in Current Chemistry

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“…[147] In bahnbrechenden Arbeiten von Seemans Gruppe wurden auch künstliche DNA-Knoten vorgestellt. [148] [149][150][151] Das erste Protein, in dem ein verknotetes Rückgrat identifiziert wurde,w ar eine a-Carboanhydrase. [152] Dieses Protein ist zu einem losen Kleeblattknoten gebunden, es müssen allerdings nur wenige Reste von einem der Termini entfernt werden, um das Protein zu entknoten, weshalb vorgeschlagen wurde dass das Protein nur einen "Einleitungsknoten" formt.…”

Section: Knoten In Dnaunclassified

Molekulare Knoten

Fielden¹,

Leigh²,

Woltering³

2017

Angewandte Chemie

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Der erste synthetische Kleeblattknoten wurde in den späten 1980er Jahren hergestellt. Kompliziertere Knotentopologien wurden jedoch erst in den letzten Jahren in molekularer Form erhalten. Die Verknotung molekularer Stränge erzeugt sterische Einschränkungen und kann so wichtige physikalische und chemische Eigenschaften verleihen, unter anderem Chiralität, starkes und selektives Binden von Ionen und katalytische Aktivität. Da die Anzahl und Komplexität molekularer Knoten steigt, wird es für Chemiker immer wichtiger, die Knotennomenklatur anderer Disziplinen zu verwenden. Hier geben wir einen Überblick über die Synthesestrategien für molekulare Knoten und beschreiben die Grundlagen der Knoten‐, Zopf‐ und Tangle‐Theorie in einem für Chemiker und molekulare Strukturen angemessenen Umfang.

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Knots in Proteins

Cited by 111 publications

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Topological knots and links in proteins

Topological knots and links in proteins

Molecular Knots

Molekulare Knoten

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