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| | ==His 62 mutant of the lectin binding domain of Lectinolysin complexed with Lewis b== | | ==His 62 mutant of the lectin binding domain of Lectinolysin complexed with Lewis b== |
| - | <StructureSection load='4gwj' size='340' side='right' caption='[[4gwj]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='4gwj' size='340' side='right'caption='[[4gwj]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gwj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_49456 Atcc 49456]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GWJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GWJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gwj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_mitis Streptococcus mitis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GWJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GWJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900123:Lewis+B+antigen,+beta+anomer'>PRD_900123</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lek|3lek]], [[3leg|3leg]], [[3leo|3leo]], [[3lei|3lei]], [[4gwi|4gwi]]</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=4gwj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwj OCA], [https://pdbe.org/4gwj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gwj RCSB], [https://www.ebi.ac.uk/pdbsum/4gwj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwj ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">samhpaf ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28037 ATCC 49456])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gwj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwj OCA], [http://pdbe.org/4gwj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gwj RCSB], [http://www.ebi.ac.uk/pdbsum/4gwj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q2PHL4_STRMT Q2PHL4_STRMT] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 49456]] | + | [[Category: Large Structures]] |
| - | [[Category: Feil, S C]] | + | [[Category: Streptococcus mitis]] |
| - | [[Category: Cholesterol-dependent cytolysin]] | + | [[Category: Feil SC]] |
| - | [[Category: F-type lectin]]
| + | |
| - | [[Category: Glycan binding]]
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| - | [[Category: Lewis antigen]]
| + | |
| - | [[Category: Sugar binding protein]]
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| Structural highlights
4gwj is a 1 chain structure with sequence from Streptococcus mitis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q2PHL4_STRMT
Publication Abstract from PubMed
The cholesterol-dependent cytolysins (CDCs) attack cells by punching large holes in their membranes. Lectinolysin from Streptococcus mitis is unique among CDCs due to the presence of an N-terminal lectin domain that enhances the pore-forming activity of the toxin. We recently determined the crystal structures of the lectin domain in complex with various glycans. These structures revealed the molecular basis for the Lewis antigen specificity of the toxin. Based on this information we have used in silico molecular modeling to design a mutant toxin, which we predicted would increase its specificity for Lewis y, an antigen found on the surface of cancer cells. Surprisingly, we found by surface plasmon resonance binding experiments that the resultant mutant lectin domain exhibited higher specificity for Lewis b antigens instead. We then undertook comparative crystallographic and molecular dynamics simulation studies of the wild-type and mutant lectin domains to understand the molecular basis for the disparity between the theoretical and experimental results. The crystallographic results revealed that the net number of interactions between Lewis y and wild-type versus mutant was unchanged whereas there was a loss of a hydrogen bond between mutant and Lewis b compared to wild-type. In contrast, the molecular dynamics studies revealed that the Lewis b antigen spent more time in the binding pocket of the mutant compared to wild-type and the reverse was true for Lewis y. The results of these simulation studies are consistent with the conclusions drawn from the surface plasmon resonance studies. This work is part of a program to engineer lectinolysin so that it will target and kill specific cells in human diseases.
Manipulating the Lewis antigen specificity of the cholesterol-dependent cytolysin lectinolysin.,Lawrence SL, Feil SC, Holien JK, Kuiper MJ, Doughty L, Dolezal O, Mulhern TD, Tweten RK, Parker MW Front Immunol. 2012 Nov 5;3:330. doi: 10.3389/fimmu.2012.00330. eCollection 2012. PMID:23181061[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lawrence SL, Feil SC, Holien JK, Kuiper MJ, Doughty L, Dolezal O, Mulhern TD, Tweten RK, Parker MW. Manipulating the Lewis antigen specificity of the cholesterol-dependent cytolysin lectinolysin. Front Immunol. 2012 Nov 5;3:330. doi: 10.3389/fimmu.2012.00330. eCollection 2012. PMID:23181061 doi:http://dx.doi.org/10.3389/fimmu.2012.00330
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