Identification of <i>Aethina tumida</i> Kir Channels as Putative Targets of the Bee Venom Peptide Tertiapin Using Structure-Based Virtual Screening Methods
Venoms are comprised of diverse mixtures of proteins, peptides, and small molecules. Identifying individual venom components and their target(s) with mechanism of action is now attainable to understand comprehensively the effectiveness of venom cocktails and how they collectively function in the def...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-09-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/9/546 |
| _version_ | 1828117467090649088 |
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| author | Craig A. Doupnik |
| author_facet | Craig A. Doupnik |
| author_sort | Craig A. Doupnik |
| collection | DOAJ |
| description | Venoms are comprised of diverse mixtures of proteins, peptides, and small molecules. Identifying individual venom components and their target(s) with mechanism of action is now attainable to understand comprehensively the effectiveness of venom cocktails and how they collectively function in the defense and predation of an organism. Here, structure-based computational methods were used with bioinformatics tools to screen and identify potential biological targets of tertiapin (TPN), a venom peptide from <i>Apis mellifera</i> (European honey bee). The small hive beetle (<i>Aethina tumida</i> (<i>A. tumida</i>)) is a natural predator of the honey bee colony and was found to possess multiple inwardly rectifying K<sup>+</sup> (Kir) channel subunit genes from a genomic BLAST search analysis. Structure-based virtual screening of homology modelled <i>A. tumida</i> Kir (<i>at</i>Kir) channels found TPN to interact with a docking profile and interface “footprint” equivalent to known TPN-sensitive mammalian Kir channels. The results support the hypothesis that <i>at</i>Kir channels, and perhaps other insect Kir channels, are natural biological targets of TPN that help defend the bee colony from infestations by blocking K<sup>+</sup> transport via <i>at</i>Kir channels. From these in silico findings, this hypothesis can now be subsequently tested in vitro by validating <i>at</i>Kir channel block as well as in vivo TPN toxicity towards <i>A. tumida</i>. This study highlights the utility and potential benefits of screening in virtual space for venom peptide interactions and their biological targets, which otherwise would not be feasible. |
| first_indexed | 2024-04-11T13:14:46Z |
| format | Article |
| id | doaj.art-6bc39bea889a4b4392c5110cc4e0f690 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T13:14:46Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-6bc39bea889a4b4392c5110cc4e0f6902022-12-22T04:22:25ZengMDPI AGToxins2072-66512019-09-0111954610.3390/toxins11090546toxins11090546Identification of <i>Aethina tumida</i> Kir Channels as Putative Targets of the Bee Venom Peptide Tertiapin Using Structure-Based Virtual Screening MethodsCraig A. Doupnik0Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, FL 33612, USAVenoms are comprised of diverse mixtures of proteins, peptides, and small molecules. Identifying individual venom components and their target(s) with mechanism of action is now attainable to understand comprehensively the effectiveness of venom cocktails and how they collectively function in the defense and predation of an organism. Here, structure-based computational methods were used with bioinformatics tools to screen and identify potential biological targets of tertiapin (TPN), a venom peptide from <i>Apis mellifera</i> (European honey bee). The small hive beetle (<i>Aethina tumida</i> (<i>A. tumida</i>)) is a natural predator of the honey bee colony and was found to possess multiple inwardly rectifying K<sup>+</sup> (Kir) channel subunit genes from a genomic BLAST search analysis. Structure-based virtual screening of homology modelled <i>A. tumida</i> Kir (<i>at</i>Kir) channels found TPN to interact with a docking profile and interface “footprint” equivalent to known TPN-sensitive mammalian Kir channels. The results support the hypothesis that <i>at</i>Kir channels, and perhaps other insect Kir channels, are natural biological targets of TPN that help defend the bee colony from infestations by blocking K<sup>+</sup> transport via <i>at</i>Kir channels. From these in silico findings, this hypothesis can now be subsequently tested in vitro by validating <i>at</i>Kir channel block as well as in vivo TPN toxicity towards <i>A. tumida</i>. This study highlights the utility and potential benefits of screening in virtual space for venom peptide interactions and their biological targets, which otherwise would not be feasible.https://www.mdpi.com/2072-6651/11/9/546bee venombioinformaticscomputational dockinghomology modellingion channel structureprotein–peptide interactionstertiapinvenom peptidesvirtual screeningsmall hive beetle |
| spellingShingle | Craig A. Doupnik Identification of <i>Aethina tumida</i> Kir Channels as Putative Targets of the Bee Venom Peptide Tertiapin Using Structure-Based Virtual Screening Methods Toxins bee venom bioinformatics computational docking homology modelling ion channel structure protein–peptide interactions tertiapin venom peptides virtual screening small hive beetle |
| title | Identification of <i>Aethina tumida</i> Kir Channels as Putative Targets of the Bee Venom Peptide Tertiapin Using Structure-Based Virtual Screening Methods |
| title_full | Identification of <i>Aethina tumida</i> Kir Channels as Putative Targets of the Bee Venom Peptide Tertiapin Using Structure-Based Virtual Screening Methods |
| title_fullStr | Identification of <i>Aethina tumida</i> Kir Channels as Putative Targets of the Bee Venom Peptide Tertiapin Using Structure-Based Virtual Screening Methods |
| title_full_unstemmed | Identification of <i>Aethina tumida</i> Kir Channels as Putative Targets of the Bee Venom Peptide Tertiapin Using Structure-Based Virtual Screening Methods |
| title_short | Identification of <i>Aethina tumida</i> Kir Channels as Putative Targets of the Bee Venom Peptide Tertiapin Using Structure-Based Virtual Screening Methods |
| title_sort | identification of i aethina tumida i kir channels as putative targets of the bee venom peptide tertiapin using structure based virtual screening methods |
| topic | bee venom bioinformatics computational docking homology modelling ion channel structure protein–peptide interactions tertiapin venom peptides virtual screening small hive beetle |
| url | https://www.mdpi.com/2072-6651/11/9/546 |
| work_keys_str_mv | AT craigadoupnik identificationofiaethinatumidaikirchannelsasputativetargetsofthebeevenompeptidetertiapinusingstructurebasedvirtualscreeningmethods |