7kmv: Difference between revisions
New page: '''Unreleased structure''' The entry 7kmv is ON HOLD Authors: Meagher, J.L., Stuckey, J.A. Description: Structure of Malaysian Banana Lectin F84T Category: Unreleased Structures [[... |
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The | ==Structure of Malaysian Banana Lectin F84T== | ||
<StructureSection load='7kmv' size='340' side='right'caption='[[7kmv]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7kmv]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Musa_acuminata Musa acuminata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KMV FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7kmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kmv OCA], [https://pdbe.org/7kmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kmv RCSB], [https://www.ebi.ac.uk/pdbsum/7kmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kmv ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lectins, carbohydrate-binding proteins, have been regarded as potential antiviral agents, as some can bind glycans on viral surface glycoproteins and inactivate their functions. However, clinical development of lectins has been stalled by the mitogenicity of many of these proteins, which is the ability to stimulate deleterious proliferation, especially of immune cells. We previously demonstrated that the mitogenic and antiviral activities of a lectin (banana lectin, BanLec) can be separated via a single amino acid mutation, histidine to threonine at position 84 (H84T), within the third Greek key. The resulting lectin, H84T BanLec, is virtually non-mitogenic but retains antiviral activity. Decreased mitogenicity was associated with disruption of pi-pi stacking between two aromatic amino acids. To examine whether we could provide further proof-of-principle of the ability to separate these two distinct lectin functions, we identified another lectin, Malaysian banana lectin (Malay BanLec), with similar structural features as BanLec, including pi-pi stacking, but with only 63% amino acid identity, and showed that it is both mitogenic and potently antiviral. We then engineered an F84T mutation expected to disrupt pi-pi stacking, analogous to H84T. As predicted, F84T Malay BanLec (F84T) was less mitogenic than wild type. However, F84T maintained strong antiviral activity and inhibited replication of HIV, Ebola, and other viruses. The F84T mutation disrupted pi-pi stacking without disrupting the overall lectin structure. These findings show that pi-pi stacking in the third Greek key is a conserved mitogenic motif in these two jacalin-related lectins BanLec and Malay BanLec, and further highlight the potential to rationally engineer antiviral lectins for therapeutic purposes. | |||
Targeted disruption of pi-pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity.,Coves-Datson EM, King SR, Legendre M, Swanson MD, Gupta A, Claes S, Meagher JL, Boonen A, Zhang L, Kalveram B, Raglow Z, Freiberg AN, Prichard M, Stuckey JA, Schols D, Markovitz DM Sci Rep. 2021 Jan 12;11(1):656. doi: 10.1038/s41598-020-80577-7. PMID:33436903<ref>PMID:33436903</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Meagher | <div class="pdbe-citations 7kmv" style="background-color:#fffaf0;"></div> | ||
[[Category: Stuckey | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Musa acuminata]] | |||
[[Category: Meagher JL]] | |||
[[Category: Stuckey JA]] | |||
Latest revision as of 18:28, 18 October 2023
Structure of Malaysian Banana Lectin F84TStructure of Malaysian Banana Lectin F84T
Structural highlights
Publication Abstract from PubMedLectins, carbohydrate-binding proteins, have been regarded as potential antiviral agents, as some can bind glycans on viral surface glycoproteins and inactivate their functions. However, clinical development of lectins has been stalled by the mitogenicity of many of these proteins, which is the ability to stimulate deleterious proliferation, especially of immune cells. We previously demonstrated that the mitogenic and antiviral activities of a lectin (banana lectin, BanLec) can be separated via a single amino acid mutation, histidine to threonine at position 84 (H84T), within the third Greek key. The resulting lectin, H84T BanLec, is virtually non-mitogenic but retains antiviral activity. Decreased mitogenicity was associated with disruption of pi-pi stacking between two aromatic amino acids. To examine whether we could provide further proof-of-principle of the ability to separate these two distinct lectin functions, we identified another lectin, Malaysian banana lectin (Malay BanLec), with similar structural features as BanLec, including pi-pi stacking, but with only 63% amino acid identity, and showed that it is both mitogenic and potently antiviral. We then engineered an F84T mutation expected to disrupt pi-pi stacking, analogous to H84T. As predicted, F84T Malay BanLec (F84T) was less mitogenic than wild type. However, F84T maintained strong antiviral activity and inhibited replication of HIV, Ebola, and other viruses. The F84T mutation disrupted pi-pi stacking without disrupting the overall lectin structure. These findings show that pi-pi stacking in the third Greek key is a conserved mitogenic motif in these two jacalin-related lectins BanLec and Malay BanLec, and further highlight the potential to rationally engineer antiviral lectins for therapeutic purposes. Targeted disruption of pi-pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity.,Coves-Datson EM, King SR, Legendre M, Swanson MD, Gupta A, Claes S, Meagher JL, Boonen A, Zhang L, Kalveram B, Raglow Z, Freiberg AN, Prichard M, Stuckey JA, Schols D, Markovitz DM Sci Rep. 2021 Jan 12;11(1):656. doi: 10.1038/s41598-020-80577-7. PMID:33436903[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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