4pit: Difference between revisions
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==Crystal Structure of Banana Lectin H84T bound to dimannose== | |||
<StructureSection load='4pit' size='340' side='right'caption='[[4pit]], [[Resolution|resolution]] 1.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4pit]] is a 4 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=4PIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PIT 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]] 1.55Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=PRD_900111:2alpha-alpha-mannobiose'>PRD_900111</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=4pit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pit OCA], [https://pdbe.org/4pit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pit RCSB], [https://www.ebi.ac.uk/pdbsum/4pit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pit ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/O22321_MUSAC O22321_MUSAC] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino-acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity, while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions. On the other hand, monovalent interactions and antiviral activity are preserved by retaining other wild-type conformational features and possibly through unique contacts involving the T84 side chain. Through such fine-tuning, target selection and downstream effects of a lectin can be modulated so as to knock down one activity, while preserving another, thus providing tools for therapeutics and for understanding the Sugar Code. | |||
Engineering a therapeutic lectin by uncoupling mitogenicity from antiviral activity.,Swanson MD, Boudreaux DM, Salmon L, Chugh J, Winter HC, Meagher JL, Andre S, Murphy PV, Oscarson S, Roy R, King S, Kaplan MH, Goldstein IJ, Tarbet EB, Hurst BL, Smee DF, de la Fuente C, Hoffmann HH, Xue Y, Rice CM, Schols D, Garcia JV, Stuckey JA, Gabius HJ, Al-Hashimi HM, Markovitz DM Cell. 2015 Oct 22;163(3):746-58. doi: 10.1016/j.cell.2015.09.056. Epub 2015 Oct, 22. PMID:26496612<ref>PMID:26496612</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4pit" style="background-color:#fffaf0;"></div> | ||
[[Category: Meagher | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Musa acuminata]] | |||
[[Category: Meagher JL]] | |||
[[Category: Stuckey JA]] | |||
Latest revision as of 03:44, 28 December 2023
Crystal Structure of Banana Lectin H84T bound to dimannoseCrystal Structure of Banana Lectin H84T bound to dimannose
Structural highlights
FunctionPublication Abstract from PubMedA key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino-acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity, while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions. On the other hand, monovalent interactions and antiviral activity are preserved by retaining other wild-type conformational features and possibly through unique contacts involving the T84 side chain. Through such fine-tuning, target selection and downstream effects of a lectin can be modulated so as to knock down one activity, while preserving another, thus providing tools for therapeutics and for understanding the Sugar Code. Engineering a therapeutic lectin by uncoupling mitogenicity from antiviral activity.,Swanson MD, Boudreaux DM, Salmon L, Chugh J, Winter HC, Meagher JL, Andre S, Murphy PV, Oscarson S, Roy R, King S, Kaplan MH, Goldstein IJ, Tarbet EB, Hurst BL, Smee DF, de la Fuente C, Hoffmann HH, Xue Y, Rice CM, Schols D, Garcia JV, Stuckey JA, Gabius HJ, Al-Hashimi HM, Markovitz DM Cell. 2015 Oct 22;163(3):746-58. doi: 10.1016/j.cell.2015.09.056. Epub 2015 Oct, 22. PMID:26496612[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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