4gwi - Revision history

OCA at 08:51, 20 March 2024

OCA — Wed, 20 Mar 2024 08:51:36 GMT

←Older revision		Revision as of 08:51, 20 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4gwi]] 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=4GWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GWI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4gwi]] 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=4GWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GWI FirstGlance]. <br>
-	</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900054:Lewis+Y+antigen,+beta+anomer'>PRD_900054</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.6Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900054:Lewis+Y+antigen,+beta+anomer'>PRD_900054</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=4gwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwi OCA], [https://pdbe.org/4gwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gwi RCSB], [https://www.ebi.ac.uk/pdbsum/4gwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwi ProSAT]</span></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=4gwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwi OCA], [https://pdbe.org/4gwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gwi RCSB], [https://www.ebi.ac.uk/pdbsum/4gwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwi ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/Q2PHL4_STRMT Q2PHL4_STRMT]		[https://www.uniprot.org/uniprot/Q2PHL4_STRMT Q2PHL4_STRMT]
-	<div style="background-color:#fffaf0;">
-	== 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<ref>PMID:23181061</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4gwi" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:23, 26 October 2022

OCA — Wed, 26 Oct 2022 07:23:02 GMT

←Older revision		Revision as of 07:23, 26 October 2022
Line 1:		Line 1:

	==His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y==		==His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y==
-	<StructureSection load='4gwi' size='340' side='right' caption='[[4gwi]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='4gwi' size='340' side='right'caption='[[4gwi]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gwi]] 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=4GWI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4GWI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gwi]] 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=4GWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GWI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~BDZ~~:~~6-DEOXY-~~ALPHA-L-~~GALACTOPYRANOSYL-(1- 3)-[6-DEOXY-ALPHA-L-GALACTOPYRANOSYL-(1- 2)-BETA-D-GALACTOPYRANOSYL-(1- 4)]-2-(ACETYLAMINO)-2-DEOXY-BETA-D-GLUCOPYRANOSE~~'>~~BDZ~~</scene>, <scene name='pdbligand=CA:~~CALCIUM+ION~~'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900054:Lewis+Y+antigen,+beta+anomer'>PRD_900054</scene></td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b~~></td>~~<td class="sblockDat">[[3lek\|3lek]]~~, ~~[[3leg\|3leg]], [[3lei\|3lei]], [[3leo\|3leo]], [[3gwj\|3gwj]]~~<~~/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=4gwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwi OCA], [https://pdbe.org/4gwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gwi RCSB], [https://www.ebi.ac.uk/pdbsum/4gwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwi 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>	+
-	<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=4gwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwi OCA], [~~http~~://pdbe.org/4gwi PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4gwi RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4gwi PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwi 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 ==
Line 22:		Line 22:
	__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 fold]]~~	+
-	~~[[Category: Glycan binding]]~~	+
-	~~[[Category: Lewis antigen]]~~	+
-	~~[[Category: Sugar binding protein~~]]	+

OCA at 08:33, 15 November 2017

OCA — Wed, 15 Nov 2017 08:33:42 GMT

←Older revision		Revision as of 08:33, 15 November 2017
Line 1:		Line 1:
-	{{STRUCTURE_4gwi\| PDB=4gwi \| SCENE= }}
-	===His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y===
-	{{ABSTRACT_PUBMED_23181061}}

-	==~~About this Structure~~==	+	==His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y==
-	[[4gwi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Dsm_12643 Dsm 12643~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GWI OCA].	+	<StructureSection load='4gwi' size='340' side='right' caption='[[4gwi]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4gwi]] 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=4GWI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GWI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BDZ:6-DEOXY-ALPHA-L-GALACTOPYRANOSYL-(1- 3)-[6-DEOXY-ALPHA-L-GALACTOPYRANOSYL-(1- 2)-BETA-D-GALACTOPYRANOSYL-(1- 4)]-2-(ACETYLAMINO)-2-DEOXY-BETA-D-GLUCOPYRANOSE'>BDZ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3lek\|3lek]], [[3leg\|3leg]], [[3lei\|3lei]], [[3leo\|3leo]], [[3gwj\|3gwj]]</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>
		+	<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=4gwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwi OCA], [http://pdbe.org/4gwi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gwi RCSB], [http://www.ebi.ac.uk/pdbsum/4gwi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwi ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== 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.

-	~~==Reference==~~	+	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<ref>PMID:23181061</ref>
-	<ref ~~group="xtra"~~>PMID:~~023181061~~</ref><~~references group~~="~~xtra~~"/><references/>	+
-	[[Category: ~~Dsm 12643~~]]	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: Feil, S C.]]	+	</div>
		+	<div class="pdbe-citations 4gwi" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Atcc 49456]]
		+	[[Category: Feil, S C]]
	[[Category: Cholesterol-dependent cytolysin]]		[[Category: Cholesterol-dependent cytolysin]]
	[[Category: F-type lectin fold]]		[[Category: F-type lectin fold]]

OCA at 13:51, 12 March 2014

OCA — Wed, 12 Mar 2014 13:51:13 GMT

←Older revision		Revision as of 13:51, 12 March 2014
Line 1:		Line 1:
-	[[Image:4gwi.jpg\|left\|200px]]
-
	{{STRUCTURE_4gwi\| PDB=4gwi \| SCENE= }}		{{STRUCTURE_4gwi\| PDB=4gwi \| SCENE= }}
-
	===His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y===		===His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y===
		+	{{ABSTRACT_PUBMED_23181061}}

		+	==About this Structure==
		+	[[4gwi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dsm_12643 Dsm 12643]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GWI OCA].

-	==~~About this Structure~~==	+	==Reference==
-	~~[[4gwi]] is a 1 chain structure with sequence from [http~~://~~en.wikipedia.org~~/~~wiki/Streptococcus_mitis Streptococcus mitis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GWI OCA].~~	+	<ref group="xtra">PMID:023181061</ref><references group="xtra"/><references/>
-	[[Category: ~~Streptococcus mitis~~]]	+	[[Category: Dsm 12643]]
	[[Category: Feil, S C.]]		[[Category: Feil, S C.]]
	[[Category: Cholesterol-dependent cytolysin]]		[[Category: Cholesterol-dependent cytolysin]]

OCA at 09:47, 21 November 2012

OCA — Wed, 21 Nov 2012 09:47:32 GMT

←Older revision		Revision as of 09:47, 21 November 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4gwi.jpg\|left\|200px]]

-	~~The entry~~ 4gwi ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4gwi\| PDB=4gwi \| SCENE= }}

-	~~Authors: Feil, S.C.~~	+	===His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y===

-	~~Description~~: ~~His 62 mutant of the~~ lectin binding ~~domain of lectinolysin complexed with~~ Lewis y	+
		+	==About this Structure==
		+	[[4gwi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptococcus_mitis Streptococcus mitis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GWI OCA].
		+	[[Category: Streptococcus mitis]]
		+	[[Category: Feil, S C.]]
		+	[[Category: Cholesterol-dependent cytolysin]]
		+	[[Category: F-type lectin fold]]
		+	[[Category: Glycan binding]]
		+	[[Category: Lewis antigen]]
		+	[[Category: Sugar binding protein]]

OCA at 08:35, 31 October 2012

OCA — Wed, 31 Oct 2012 08:35:54 GMT

←Older revision		Revision as of 08:35, 31 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4gwi is ON HOLD	+	The entry 4gwi is ON HOLD until Paper Publication

	Authors: Feil, S.C.		Authors: Feil, S.C.

	Description: His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y		Description: His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y

OCA: Protected "4gwi" [edit=sysop:move=sysop]

OCA — Wed, 12 Sep 2012 04:54:40 GMT

Protected "4gwi" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:54, 12 September 2012

OCA: New page: '''Unreleased structure''' The entry 4gwi is ON HOLD Authors: Feil, S.C. Description: His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y

OCA — Wed, 12 Sep 2012 04:54:39 GMT

New page: '''Unreleased structure''' The entry 4gwi is ON HOLD Authors: Feil, S.C. Description: His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y

New page

'''Unreleased structure'''

The entry 4gwi is ON HOLD

Authors: Feil, S.C.

Description: His 62 mutant of the lectin binding domain of lectinolysin complexed with Lewis y