5tkc - Revision history

OCA at 09:26, 23 October 2024

2024-10-23T09:26:01Z

← Older revision		Revision as of 09:26, 23 October 2024
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	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/~~Q8I8I2_TOXGO Q8I8I2_TOXGO~~]		[https://www.uniprot.org/uniprot/ALF1_TOXGO ALF1_TOXGO] Plays a key role in glycolysis by catalyzing the cleavage of fructose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (PubMed:19380114, PubMed:25284756, PubMed:28972169). Forms a bridge between cell surface adhesins and the actin cytoskeleton (PubMed:12718875, PubMed:19380114). Required for parasite invasion of host cells (PubMed:19380114).<ref>PMID:12718875</ref> <ref>PMID:19380114</ref> <ref>PMID:25284756</ref> <ref>PMID:28972169</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Fructose-1,6-bisphosphate (FBP) aldolase, a glycolytic enzyme, catalyzes the reversible and stereospecific aldol addition of dihydroxyacetone-P (DHAP) and D-glyceraldehyde-3-P (D-G3P) by an unresolved mechanism. To afford insight into the molecular determinants of FBP aldolase stereospecificity during aldol addition, a key ternary complex formed by DHAP and D-G3P, comprising 2 % of the equilibrium population at physiological pH, was cryotrapped in the active site of Toxoplasma gondii aldolase (TgALD) crystals to high resolution. The growth of TgALD crystals in acidic conditions enabled trapping of the ternary complex as a dominant population. The obligate 3(S)-4(R) stereochemistry at the nascent C3-C4 bond of FBP requires a si-face attack by the covalent DHAP nucleophile on the D-G3P aldehyde si-face in the active site. The cis-isomer of the D-G3P aldehyde, representing the dominant population trapped in the ternary complex, would lead to re-face attack on the aldehyde and yield tagatose 1,6-bisphosphate, a competitive inhibitor of the enzyme. We propose that unhindered rotational isomerization by the D-G3P aldehyde moiety in the ternary complex generates the active trans-isomer competent for carbonyl bond activation by active-site residues, thereby enabling si-face attack by the DHAP enamine. C-C bond formation by the cis-isomer is suppressed by hydrogen-bonding of the cis-aldehyde carbonyl with the DHAP enamine phosphate dianion through a tetrahedrally coordinated water molecule. The active site geometry further suppresses C-C bond formation with the L-G3P enantiomer of D-G3P. Understanding C-C formation is of fundamental importance in biological reactions and has considerable relevance to biosynthetic reactions in organic chemistry.

			Isomer Activation Controls Stereospecificity of Class I Fructose-1,6-bisphosphate Aldolases.,Heron PW, Sygusch J J Biol Chem. 2017 Sep 27. pii: jbc.M117.811034. doi: 10.1074/jbc.M117.811034. PMID:28972169<ref>PMID:28972169</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5tkc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Aldolase 3D structures\|Aldolase 3D structures]]		*[[Aldolase 3D structures\|Aldolase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 15:41, 6 March 2024

2024-03-06T15:41:36Z

← Older revision		Revision as of 15:41, 6 March 2024
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	<StructureSection load='5tkc' size='340' side='right'caption='[[5tkc]], [[Resolution\|resolution]] 1.78Å' scene=''>		<StructureSection load='5tkc' size='340' side='right'caption='[[5tkc]], [[Resolution\|resolution]] 1.78Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5tkc]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Toxgo Toxgo~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TKC FirstGlance]. <br>		<table><tr><td colspan='2'>[[5tkc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TKC FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=13P:1,3-DIHYDROXYACETONEPHOSPHATE'>13P</scene>, <scene name='pdbligand=G3H:GLYCERALDEHYDE-3-PHOSPHATE'>G3H</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.779Å</td></tr>
	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tjs\|5tjs]]~~, [[~~5tk3~~\|~~5tk3]], [[5tkl\|5tkl]], [[5tkn\|5tkn]], [[5tkp\|5tkp~~]]</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=13P:1,3-DIHYDROXYACETONEPHOSPHATE'>13P</scene>, <scene name='pdbligand=G3H:GLYCERALDEHYDE-3-PHOSPHATE'>G3H</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~ald-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=~~5&id=5811 TOXGO])</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=5tkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkc OCA], [https://pdbe.org/5tkc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tkc RCSB], [https://www.ebi.ac.uk/pdbsum/5tkc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkc ProSAT]</span></td></tr>
	<~~tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13]~~ </~~span~~></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=5tkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkc OCA], [~~http~~://pdbe.org/5tkc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5tkc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5tkc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkc ProSAT]</span></td></tr>
	</table>		</table>
	~~<div style~~=~~"background-color:#fffaf0;">~~		== Function ==
	== ~~Publication Abstract from PubMed~~ ==		[https://www.uniprot.org/uniprot/Q8I8I2_TOXGO Q8I8I2_TOXGO]
	Fructose-1,6-bisphosphate (FBP) aldolase, a glycolytic enzyme, catalyzes the reversible and stereospecific aldol addition of dihydroxyacetone-P (DHAP) and D-glyceraldehyde-3-P (D-G3P) by an unresolved mechanism. To afford insight into the molecular determinants of FBP aldolase stereospecificity during aldol addition, a key ternary complex formed by DHAP and D-G3P, comprising 2 % of the equilibrium population at physiological pH, was cryotrapped in the active site of Toxoplasma gondii aldolase (TgALD) crystals to high resolution. The growth of TgALD crystals in acidic conditions enabled trapping of the ternary complex as a dominant population. The obligate 3(S)-4(R) stereochemistry at the nascent C3-C4 bond of FBP requires a si-face attack by the covalent DHAP nucleophile on the D-G3P aldehyde si-face in the active site. The cis-isomer of the D-G3P aldehyde, representing the dominant population trapped in the ternary complex, would lead to re-face attack on the aldehyde and yield tagatose 1,6-bisphosphate, a competitive inhibitor of the enzyme. We propose that unhindered rotational isomerization by the D-G3P aldehyde moiety in the ternary complex generates the active trans-isomer competent for carbonyl bond activation by active-site residues, thereby enabling si-face attack by the DHAP enamine. C-C bond formation by the cis-isomer is suppressed by hydrogen-bonding of the cis-aldehyde carbonyl with the DHAP enamine phosphate dianion through a tetrahedrally coordinated water molecule. The active site geometry further suppresses C-C bond formation with the L-G3P enantiomer of D-G3P. Understanding C-C formation is of fundamental importance in biological reactions and has considerable relevance to biosynthetic reactions in organic chemistry.

	Isomer Activation Controls Stereospecificity of Class I Fructose-1,6-bisphosphate Aldolases.,Heron PW, Sygusch J J Biol Chem. 2017 Sep 27. pii: jbc.M117.811034. doi: 10.1074/jbc.M117.811034. PMID:28972169<ref>PMID:~~28972169<~~/~~ref>~~

	~~From MEDLINE®~~/~~PubMed®, a database of the U~~.S. ~~National Library of Medicine.<br>~~
	</~~div>~~
	~~<div class="pdbe-citations 5tkc" style="background-color:#fffaf0;"><~~/~~div>~~

	==See Also==		==See Also==
	*[[Aldolase 3D structures\|Aldolase 3D structures]]		*[[Aldolase 3D structures\|Aldolase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Fructose-bisphosphate aldolase]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Toxgo~~]]		[[Category: Toxoplasma gondii]]
	[[Category: Heron~~, P W~~]]		[[Category: Heron PW]]
	[[Category: Sygusch, J]]		[[Category: Sygusch J]]
	~~[[Category: Aldolase]]~~
	~~[[Category: Covalent]]~~
	~~[[Category: Enamine]]~~
	~~[[Category: Glycolysis]]~~
	~~[[Category: Intermediate]]~~
	~~[[Category: Lyase]]~~
	~~[[Category: Substrate]]~~
	~~[[Category: Tim barrel~~]]

OCA at 08:18, 8 January 2020

2020-01-08T08:18:14Z

← Older revision		Revision as of 08:18, 8 January 2020
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	==Crystal structure of FBP aldolase from Toxoplasma gondii, ternary complex==		==Crystal structure of FBP aldolase from Toxoplasma gondii, ternary complex==
	<StructureSection load='5tkc' size='340' side='right' caption='[[5tkc]], [[Resolution\|resolution]] 1.78Å' scene=''>		<StructureSection load='5tkc' size='340' side='right'caption='[[5tkc]], [[Resolution\|resolution]] 1.78Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5tkc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxgo Toxgo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TKC FirstGlance]. <br>		<table><tr><td colspan='2'>[[5tkc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxgo Toxgo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TKC FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 5tkc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5tkc" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Aldolase 3D structures\|Aldolase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Fructose-bisphosphate aldolase]]		[[Category: Fructose-bisphosphate aldolase]]
			[[Category: Large Structures]]
	[[Category: Toxgo]]		[[Category: Toxgo]]
	[[Category: Heron, P W]]		[[Category: Heron, P W]]

OCA at 07:31, 13 December 2017

2017-12-13T07:31:14Z

← Older revision		Revision as of 07:31, 13 December 2017
Line 3:		Line 3:
	<StructureSection load='5tkc' size='340' side='right' caption='[[5tkc]], [[Resolution\|resolution]] 1.78Å' scene=''>		<StructureSection load='5tkc' size='340' side='right' caption='[[5tkc]], [[Resolution\|resolution]] 1.78Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5tkc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TKC FirstGlance]. <br>		<table><tr><td colspan='2'>[[5tkc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxgo Toxgo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TKC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=13P:1,3-DIHYDROXYACETONEPHOSPHATE'>13P</scene>, <scene name='pdbligand=G3H:GLYCERALDEHYDE-3-PHOSPHATE'>G3H</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=13P:1,3-DIHYDROXYACETONEPHOSPHATE'>13P</scene>, <scene name='pdbligand=G3H:GLYCERALDEHYDE-3-PHOSPHATE'>G3H</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tjs\|5tjs]], [[5tk3\|5tk3]], [[5tkl\|5tkl]], [[5tkn\|5tkn]], [[5tkp\|5tkp]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tjs\|5tjs]], [[5tk3\|5tk3]], [[5tkl\|5tkl]], [[5tkn\|5tkn]], [[5tkp\|5tkp]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ald-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5811 TOXGO])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] </span></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=5tkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkc OCA], [http://pdbe.org/5tkc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tkc RCSB], [http://www.ebi.ac.uk/pdbsum/5tkc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkc ProSAT]</span></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=5tkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkc OCA], [http://pdbe.org/5tkc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tkc RCSB], [http://www.ebi.ac.uk/pdbsum/5tkc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkc ProSAT]</span></td></tr>
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	</StructureSection>		</StructureSection>
	[[Category: Fructose-bisphosphate aldolase]]		[[Category: Fructose-bisphosphate aldolase]]
			[[Category: Toxgo]]
	[[Category: Heron, P W]]		[[Category: Heron, P W]]
	[[Category: Sygusch, J]]		[[Category: Sygusch, J]]

OCA at 06:59, 18 October 2017

2017-10-18T06:59:39Z

@@ Line 1: / Line 1: @@
-The entry 5tkc is ON HOLD  until Paper Publication
+==Crystal structure of FBP aldolase from Toxoplasma gondii, ternary complex==
-Authors: Heron, P.W., Sygusch, J.
+Isomer Activation Controls Stereospecificity of Class I Fructose-1,6-bisphosphate Aldolases.,Heron PW, Sygusch J J Biol Chem. 2017 Sep 27. pii: jbc.M117.811034. doi: 10.1074/jbc.M117.811034. PMID:28972169<ref>PMID:28972169</ref>
-Description: Crystal structure of FBP aldolase from Toxoplasma gondii, ternary complex
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Heron, P.W]]
+<div class="pdbe-citations 5tkc" style="background-color:#fffaf0;"></div>
 [[Category: Sygusch, J]]

OCA at 17:09, 26 October 2016

2016-10-26T17:09:30Z

← Older revision		Revision as of 17:09, 26 October 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5tkc is ON HOLD		The entry 5tkc is ON HOLD until Paper Publication

	Authors: Heron, P.W., Sygusch, J.		Authors: Heron, P.W., Sygusch, J.

OCA: Protected "5tkc" [edit=sysop:move=sysop]

2016-10-19T15:57:38Z

Protected "5tkc" [edit=sysop:move=sysop]

← Older revision	Revision as of 15:57, 19 October 2016
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5tkc is ON HOLD Authors: Heron, P.W., Sygusch, J. Description: Crystal structure of FBP aldolase from Toxoplasma gondii, ternary complex [[Category...

2016-10-19T15:57:37Z

New page: '''Unreleased structure''' The entry 5tkc is ON HOLD Authors: Heron, P.W., Sygusch, J. Description: Crystal structure of FBP aldolase from Toxoplasma gondii, ternary complex [[Category...

New page

'''Unreleased structure'''

The entry 5tkc is ON HOLD

Authors: Heron, P.W., Sygusch, J.

Description: Crystal structure of FBP aldolase from Toxoplasma gondii, ternary complex
[[Category: Unreleased Structures]]
[[Category: Heron, P.W]]
[[Category: Sygusch, J]]