The First Snake Venom KTS/Disintegrins-Integrin Interactions Using Bioinformatics Approaches

Abstract

Snake venom contains a number of active molecules that have been shown to possess high anti-tumor activities; disintegrins are an excellent example among these. Their ability to interact and bind with integrins suggests that they could be very valuable molecules for the development of new cancer therapeutic approaches. However, in the absence of a clear Lysine-Threonine-Serine (KTS) Disintegrins Integrin interaction model, the exact compound features behind it are still unknown. In this study, we investigated the structural characteristics of three KTS-disintegrins and the interaction mechanisms with the α1β1 integrin receptor using in silico bioinformatics approaches. Normal mode analysis showed that the flexibility of the KTSR motif and the C-terminal region play a key role and influence the KTS-Disintegrin-integrin interaction. Protein-protein docking also suggested that the interaction involving the KTSR motif is highly dependent on the residue following K21, S23 and R24. These findings contribute to a better understanding of the KTS-Disintegrin-Integrin structural differences and their interactions with α1β1 receptors, which could improve the selection process of the best active molecules for antitumor therapies.

Venomics and Peptidomics of Palearctic vipers: Clade-wide analysis of seven taxa of the generaVipera,Montivipera,MacroviperaandDaboiaacross Türkiye

“…It should be emphasized that Macrovipera has the largest DI amount of the four genera with a consistently high content of 11-16%, independently to the DI subfamily composition. Although the expected monomeric, KTS sequence containing short DI obtustatin was originally characterized as high abundant toxin of M. l. obtusa (unreported local origin) with 7% of the whole venom proteome, no short nor monomeric DI has been described until now for any Turkish and Iranian Macrovipera venom 129,131 , while several R/KTS DI are even known from other Viperidae venoms, including recently Vipera 114,132 . Similarly, the venoms of another Turkish M. l. obtusa location and an Iranian M. l. cernovi lack small DI, while the Russian and Armenian M. l. obtusa contain them 129 .…”

Venomics and Peptidomics of Palearctic Vipers: A Clade-Wide Analysis of Seven Taxa of the Genera Vipera, Montivipera, Macrovipera, and Daboia across Türkiye

“…Although the expected monomeric, KTS sequence containing short DI obtustatin was originally characterized as high abundant toxin of M. l. obtusa (unreported local origin) with 7% of the whole venom proteome, no short nor monomeric DI has been described until now for any Turkish and Iranian Macrovipera venom, , while several R/KTS DI are known from other Viperidae venoms, including recently Vipera. , Similarly, the venoms of another Turkish M. l. obtusa location and an Iranian M.…”