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| | <StructureSection load='2x13' size='340' side='right'caption='[[2x13]], [[Resolution|resolution]] 1.74Å' scene=''> | | <StructureSection load='2x13' size='340' side='right'caption='[[2x13]], [[Resolution|resolution]] 1.74Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2x13]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X13 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2x13]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X13 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PG:3-PHOSPHOGLYCERIC+ACID'>3PG</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.74Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2xe7|2xe7]], [[2y3i|2y3i]], [[2wzb|2wzb]], [[2xe6|2xe6]], [[2wzc|2wzc]], [[2x14|2x14]], [[2x15|2x15]], [[2wzd|2wzd]], [[2xe8|2xe8]]</div></td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphoglycerate_kinase Phosphoglycerate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.2.3 2.7.2.3] </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=2x13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x13 OCA], [https://pdbe.org/2x13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x13 RCSB], [https://www.ebi.ac.uk/pdbsum/2x13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x13 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=2x13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x13 OCA], [https://pdbe.org/2x13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x13 RCSB], [https://www.ebi.ac.uk/pdbsum/2x13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x13 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/PGK1_HUMAN PGK1_HUMAN]] Defects in PGK1 are the cause of phosphoglycerate kinase 1 deficiency (PGK1D) [MIM:[https://omim.org/entry/300653 300653]]. It is a condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations.<ref>PMID:8673469</ref> <ref>PMID:8043870</ref> <ref>PMID:8615693</ref> <ref>PMID:9744480</ref> <ref>PMID:2001457</ref> <ref>PMID:1586722</ref> <ref>PMID:1547346</ref> <ref>PMID:6941312</ref> <ref>PMID:6933565</ref>
| + | [https://www.uniprot.org/uniprot/PGK1_HUMAN PGK1_HUMAN] Defects in PGK1 are the cause of phosphoglycerate kinase 1 deficiency (PGK1D) [MIM:[https://omim.org/entry/300653 300653]. It is a condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations.<ref>PMID:8673469</ref> <ref>PMID:8043870</ref> <ref>PMID:8615693</ref> <ref>PMID:9744480</ref> <ref>PMID:2001457</ref> <ref>PMID:1586722</ref> <ref>PMID:1547346</ref> <ref>PMID:6941312</ref> <ref>PMID:6933565</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PGK1_HUMAN PGK1_HUMAN]] In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein).
| + | [https://www.uniprot.org/uniprot/PGK1_HUMAN PGK1_HUMAN] In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein). |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Enzymes facilitating the transfer of phosphate groups constitute the most extensive protein families across all kingdoms of life. They make up approximately 10% of the proteins found in the human genome. Understanding the mechanisms by which enzymes catalyze these reactions is essential in characterizing the processes they regulate. Metal fluorides can be used as multifunctional tools to study these enzymes. These ionic species bear the same charge as phosphate and the transferring phosphoryl group and, in addition, allow the enzyme to be trapped in catalytically important states with spectroscopically sensitive atoms interacting directly with active site residues. The ionic nature of these phosphate surrogates also allows their removal and replacement with other analogs. Here, we describe the best practices to obtain these complexes, their use in NMR, X-ray crystallography, cryo-EM, and SAXS and describe a new metal fluoride, scandium tetrafluoride, which has significant anomalous signal using soft X-rays. |
| | + | |
| | + | Metal fluorides-multi-functional tools for the study of phosphoryl transfer enzymes, a practical guide.,Pellegrini E, Juyoux P, von Velsen J, Baxter NJ, Dannatt HRW, Jin Y, Cliff MJ, Waltho JP, Bowler MW Structure. 2024 Jul 22:S0969-2126(24)00270-3. doi: 10.1016/j.str.2024.07.007. PMID:39106858<ref>PMID:39106858</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2x13" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphoglycerate kinase]]
| + | [[Category: Baxter NJ]] |
| - | [[Category: Baxter, N J]] | + | [[Category: Blackburn GM]] |
| - | [[Category: Blackburn, G M]] | + | [[Category: Bowler MW]] |
| - | [[Category: Bowler, M W]] | + | [[Category: Cliff MJ]] |
| - | [[Category: Cliff, M J]] | + | [[Category: Hownslow AMH]] |
| - | [[Category: Hownslow, A M.H]] | + | [[Category: Marston JPM]] |
| - | [[Category: Marston, J P.M]] | + | [[Category: Szabo J]] |
| - | [[Category: Szabo, J]] | + | [[Category: Varga AV]] |
| - | [[Category: Varga, A V]] | + | [[Category: Vas M]] |
| - | [[Category: Vas, M]] | + | [[Category: Waltho JP]] |
| - | [[Category: Waltho, J P]] | + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Glycolysis]]
| + | |
| - | [[Category: Hereditary hemolytic anemia]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transition state analogue]]
| + | |
| Structural highlights
Disease
PGK1_HUMAN Defects in PGK1 are the cause of phosphoglycerate kinase 1 deficiency (PGK1D) [MIM:300653. It is a condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Function
PGK1_HUMAN In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein).
Publication Abstract from PubMed
Enzymes facilitating the transfer of phosphate groups constitute the most extensive protein families across all kingdoms of life. They make up approximately 10% of the proteins found in the human genome. Understanding the mechanisms by which enzymes catalyze these reactions is essential in characterizing the processes they regulate. Metal fluorides can be used as multifunctional tools to study these enzymes. These ionic species bear the same charge as phosphate and the transferring phosphoryl group and, in addition, allow the enzyme to be trapped in catalytically important states with spectroscopically sensitive atoms interacting directly with active site residues. The ionic nature of these phosphate surrogates also allows their removal and replacement with other analogs. Here, we describe the best practices to obtain these complexes, their use in NMR, X-ray crystallography, cryo-EM, and SAXS and describe a new metal fluoride, scandium tetrafluoride, which has significant anomalous signal using soft X-rays.
Metal fluorides-multi-functional tools for the study of phosphoryl transfer enzymes, a practical guide.,Pellegrini E, Juyoux P, von Velsen J, Baxter NJ, Dannatt HRW, Jin Y, Cliff MJ, Waltho JP, Bowler MW Structure. 2024 Jul 22:S0969-2126(24)00270-3. doi: 10.1016/j.str.2024.07.007. PMID:39106858[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yoshida A, Twele TW, Dave V, Beutler E. Molecular abnormality of a phosphoglycerate kinase variant (PGK-Alabama). Blood Cells Mol Dis. 1995;21(3):179-81. PMID:8673469 doi:S1079-9796(85)70020-4
- ↑ Cohen-Solal M, Valentin C, Plassa F, Guillemin G, Danze F, Jaisson F, Rosa R. Identification of new mutations in two phosphoglycerate kinase (PGK) variants expressing different clinical syndromes: PGK Creteil and PGK Amiens. Blood. 1994 Aug 1;84(3):898-903. PMID:8043870
- ↑ Ookawara T, Dave V, Willems P, Martin JJ, de Barsy T, Matthys E, Yoshida A. Retarded and aberrant splicings caused by single exon mutation in a phosphoglycerate kinase variant. Arch Biochem Biophys. 1996 Mar 1;327(1):35-40. PMID:8615693 doi:http://dx.doi.org/10.1006/abbi.1996.0089
- ↑ Valentin C, Birgens H, Craescu CT, Brodum-Nielsen K, Cohen-Solal M. A phosphoglycerate kinase mutant (PGK Herlev; D285V) in a Danish patient with isolated chronic hemolytic anemia: mechanism of mutation and structure-function relationships. Hum Mutat. 1998;12(4):280-7. PMID:9744480 doi:<280::AID-HUMU10>3.0.CO;2-V 10.1002/(SICI)1098-1004(1998)12:4<280::AID-HUMU10>3.0.CO;2-V
- ↑ Maeda M, Yoshida A. Molecular defect of a phosphoglycerate kinase variant (PGK-Matsue) associated with hemolytic anemia: Leu----Pro substitution caused by T/A----C/G transition in exon 3. Blood. 1991 Mar 15;77(6):1348-52. PMID:2001457
- ↑ Maeda M, Bawle EV, Kulkarni R, Beutler E, Yoshida A. Molecular abnormalities of a phosphoglycerate kinase variant generated by spontaneous mutation. Blood. 1992 May 15;79(10):2759-62. PMID:1586722
- ↑ Fujii H, Kanno H, Hirono A, Shiomura T, Miwa S. A single amino acid substitution (157 Gly----Val) in a phosphoglycerate kinase variant (PGK Shizuoka) associated with chronic hemolysis and myoglobinuria. Blood. 1992 Mar 15;79(6):1582-5. PMID:1547346
- ↑ Fujii H, Chen SH, Akatsuka J, Miwa S, Yoshida A. Use of cultured lymphoblastoid cells for the study of abnormal enzymes: molecular abnormality of a phosphoglycerate kinase variant associated with hemolytic anemia. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2587-90. PMID:6941312
- ↑ Fujii H, Yoshida A. Molecular abnormality of phosphoglycerate kinase-Uppsala associated with chronic nonspherocytic hemolytic anemia. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5461-5. PMID:6933565
- ↑ Pellegrini E, Juyoux P, von Velsen J, Baxter NJ, Dannatt HRW, Jin Y, Cliff MJ, Waltho JP, Bowler MW. Metal fluorides-multi-functional tools for the study of phosphoryl transfer enzymes, a practical guide. Structure. 2024 Jul 22:S0969-2126(24)00270-3. PMID:39106858 doi:10.1016/j.str.2024.07.007
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