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| | ==Crystal structure of FBP aldolase from Toxoplasma gondii, condensation intermediate== | | ==Crystal structure of FBP aldolase from Toxoplasma gondii, condensation intermediate== |
| - | <StructureSection load='5tkl' size='340' side='right' caption='[[5tkl]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='5tkl' size='340' side='right'caption='[[5tkl]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tkl]] 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=5TKL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TKL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tkl]] 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=5TKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TKL 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=P6F:1,6-DI-O-PHOSPHONO-D-FRUCTOSE'>P6F</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]] 1.751Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tjs|5tjs]], [[5tk3|5tk3]], [[5tkc|5tkc]], [[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=P6F:1,6-DI-O-PHOSPHONO-D-FRUCTOSE'>P6F</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=5tkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkl OCA], [https://pdbe.org/5tkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tkl RCSB], [https://www.ebi.ac.uk/pdbsum/5tkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkl 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=5tkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkl OCA], [http://pdbe.org/5tkl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tkl RCSB], [http://www.ebi.ac.uk/pdbsum/5tkl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5tkl" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5tkl" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aldolase 3D structures|Aldolase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Fructose-bisphosphate aldolase]] | + | [[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: Schiff base]]
| + | |
| - | [[Category: Substrate]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| Structural highlights
Function
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).[1] [2] [3] [4]
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jewett TJ, Sibley LD. Aldolase forms a bridge between cell surface adhesins and the actin cytoskeleton in apicomplexan parasites. Mol Cell. 2003 Apr;11(4):885-94. PMID:12718875 doi:10.1016/s1097-2765(03)00113-8
- ↑ Starnes GL, Coincon M, Sygusch J, Sibley LD. Aldolase is essential for energy production and bridging adhesin-actin cytoskeletal interactions during parasite invasion of host cells. Cell Host Microbe. 2009 Apr 23;5(4):353-64. PMID:19380114 doi:10.1016/j.chom.2009.03.005
- ↑ Tonkin ML, Halavaty AS, Ramaswamy R, Ruan J, Igarashi M, Ngo HM, Boulanger MJ. Structural and functional divergence of the aldolase fold in Toxoplasma gondii. J Mol Biol. 2014 Oct 2. pii: S0022-2836(14)00518-X. doi:, 10.1016/j.jmb.2014.09.019. PMID:25284756 doi:http://dx.doi.org/10.1016/j.jmb.2014.09.019
- ↑ Heron PW, Sygusch J. Isomer Activation Controls Stereospecificity of Class I Fructose-1,6-bisphosphate Aldolases. J Biol Chem. 2017 Sep 27. pii: jbc.M117.811034. doi: 10.1074/jbc.M117.811034. PMID:28972169 doi:http://dx.doi.org/10.1074/jbc.M117.811034
- ↑ Heron PW, Sygusch J. Isomer Activation Controls Stereospecificity of Class I Fructose-1,6-bisphosphate Aldolases. J Biol Chem. 2017 Sep 27. pii: jbc.M117.811034. doi: 10.1074/jbc.M117.811034. PMID:28972169 doi:http://dx.doi.org/10.1074/jbc.M117.811034
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