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| | <StructureSection load='6sy7' size='340' side='right'caption='[[6sy7]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='6sy7' size='340' side='right'caption='[[6sy7]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6sy7]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SY7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SY7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6sy7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SY7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BNZ:BENZENE'>BNZ</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]] 2.75Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/6-phosphofructokinase 6-phosphofructokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.11 2.7.1.11] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BNZ:BENZENE'>BNZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=6sy7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sy7 OCA], [http://pdbe.org/6sy7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sy7 RCSB], [http://www.ebi.ac.uk/pdbsum/6sy7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sy7 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=6sy7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sy7 OCA], [https://pdbe.org/6sy7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sy7 RCSB], [https://www.ebi.ac.uk/pdbsum/6sy7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sy7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PFKA_TRYBB PFKA_TRYBB]] Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[HAMAP-Rule:MF_03186] | + | [https://www.uniprot.org/uniprot/PFKA_TRYBB PFKA_TRYBB] Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[HAMAP-Rule:MF_03186] |
| | <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 6sy7" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6sy7" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phosphofructokinase 3D structures|Phosphofructokinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 6-phosphofructokinase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: McNae, I W]] | + | [[Category: Trypanosoma brucei brucei]] |
| - | [[Category: Vasquez-Valdivieso, M G]] | + | [[Category: McNae IW]] |
| - | [[Category: Walkinshaw, M D]] | + | [[Category: Vasquez-Valdivieso MG]] |
| - | [[Category: Allostery]] | + | [[Category: Walkinshaw MD]] |
| - | [[Category: Amp]]
| + | |
| - | [[Category: Glycolysis]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PFKA_TRYBB Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[HAMAP-Rule:MF_03186]
Publication Abstract from PubMed
Trypanosomatids possess glycosome organelles that contain much of the glycolytic machinery, including phosphofructokinase (PFK). We present kinetic and structural data for PFK from three human pathogenic trypanosomatids, illustrating intriguing differences that may reflect evolutionary adaptations to differing ecological niches. The activity of Leishmania PFK - to a much larger extent than Trypanosoma PFK - is reliant on AMP for activity regulation, with 1mM AMP increasing the L. infantum PFK (LiPFK) kcat/K0.5 (F6P) value by 10-fold, compared to only a 1.3- and 1.4-fold increase for T. cruzi and T. brucei PFK, respectively. We also show that Leishmania PFK melts at a significantly lower (> 15 degrees C) temperature than Trypanosoma PFKs and that addition of either AMP or ATP result in a marked stabilisation of the protein. Sequence comparisons of Trypanosoma spp. and Leishmania spp. show that divergence of the two genera involved amino acid substitutions that occur in the enzyme's 'reaching arms' and 'embracing arms' that determine tetramer stability. The dramatic effects of AMP on Leishmania activity compared with the Trypanosoma PFKs may be explained by differences between the T to R equilibria for the two families, with the low melting Leishmania PFK favouring the flexible inactive T-state in the absence of AMP. Sequence comparisons along with the enzymatic and structural data presented here also suggest there was a loss of AMP-dependent regulation in Trypanosoma species rather than gain of this characteristic in Leishmania species and that AMP acts as a key regulator in Leishmania governing the balance between glycolysis and gluconeogenesis.
Kinetic and structural studies of Trypanosoma and Leishmania phosphofructokinases show evolutionary divergence and identify AMP as a switch regulating glycolysis versus gluconeogenesis.,Fernandes PM, Kinkead J, McNae IW, Vasquez-Valdivieso M, Wear MA, Michels PAM, Walkinshaw MD FEBS J. 2019 Dec 15. doi: 10.1111/febs.15177. PMID:31838765[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fernandes PM, Kinkead J, McNae IW, Vasquez-Valdivieso M, Wear MA, Michels PAM, Walkinshaw MD. Kinetic and structural studies of Trypanosoma and Leishmania phosphofructokinases show evolutionary divergence and identify AMP as a switch regulating glycolysis versus gluconeogenesis. FEBS J. 2019 Dec 15. doi: 10.1111/febs.15177. PMID:31838765 doi:http://dx.doi.org/10.1111/febs.15177
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