View source for 2wzb


==The catalytically active fully closed conformation of human phosphoglycerate kinase in complex with ADP, 3PG and magnesium trifluoride==
<StructureSection load='2wzb' size='340' side='right'caption='[[2wzb]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wzb]] 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=2WZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WZB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.47&#8491;</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</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=2wzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wzb OCA], [https://pdbe.org/2wzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wzb RCSB], [https://www.ebi.ac.uk/pdbsum/2wzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wzb ProSAT]</span></td></tr>
</table>
== 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> 
== 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).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wz/2wzb_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wzb ConSurf].
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== Publication Abstract from PubMed ==
Transition state analogue (TSA) complexes formed by phosphoglycerate kinase (PGK) have been used to test the hypothesis that balancing of charge within the transition state dominates enzyme-catalyzed phosphoryl transfer. High-resolution structures of trifluoromagnesate (MgF(3)(-)) and tetrafluoroaluminate (AlF(4)(-)) complexes of PGK have been determined using X-ray crystallography and (19)F-based NMR methods, revealing the nature of the catalytically relevant state of this archetypal metabolic kinase. Importantly, the side chain of K219, which coordinates the alpha-phosphate group in previous ground state structures, is sequestered into coordinating the metal fluoride, thereby creating a charge environment complementary to the transferring phosphoryl group. In line with the dominance of charge balance in transition state organization, the substitution K219A induces a corresponding reduction in charge in the bound aluminum fluoride species, which changes to a trifluoroaluminate (AlF(3)(0)) complex. The AlF(3)(0) moiety retains the octahedral geometry observed within AlF(4)(-) TSA complexes, which endorses the proposal that some of the widely reported trigonal AlF(3)(0) complexes of phosphoryl transfer enzymes may have been misassigned and in reality contain MgF(3)(-).

Transition State Analogue Structures of Human Phosphoglycerate Kinase Establish the Importance of Charge Balance in Catalysis.,Cliff MJ, Bowler MW, Varga A, Marston JP, Szabo J, Hounslow AM, Baxter NJ, Blackburn GM, Vas M, Waltho JP J Am Chem Soc. 2010 Apr 19. PMID:20397725<ref>PMID:20397725</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2wzb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphoglycerate kinase 3D structures|Phosphoglycerate kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baxter NJ]]
[[Category: Blackburn GM]]
[[Category: Bowler MW]]
[[Category: Cliff MJ]]
[[Category: Hownslow AMH]]
[[Category: Marston JPM]]
[[Category: Szabo J]]
[[Category: Varga AV]]
[[Category: Vas M]]
[[Category: Waltho JP]]