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[[Image:2vgb.jpg|left|200px]]


{{Structure
==HUMAN ERYTHROCYTE PYRUVATE KINASE==
|PDB= 2vgb |SIZE=350|CAPTION= <scene name='initialview01'>2vgb</scene>, resolution 2.73&Aring;
<StructureSection load='2vgb' size='340' side='right'caption='[[2vgb]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Fbp+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Pga+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:K+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:Mn+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:Fbp+Binding+Site+For+Chain+B'>AC5</scene>, <scene name='pdbsite=AC6:Pga+Binding+Site+For+Chain+B'>AC6</scene>, <scene name='pdbsite=AC7:K+Binding+Site+For+Chain+B'>AC7</scene>, <scene name='pdbsite=AC8:Mn+Binding+Site+For+Chain+B'>AC8</scene>, <scene name='pdbsite=AC9:Fbp+Binding+Site+For+Chain+C'>AC9</scene>, <scene name='pdbsite=BC1:Pga+Binding+Site+For+Chain+C'>BC1</scene>, <scene name='pdbsite=BC2:K+Binding+Site+For+Chain+C'>BC2</scene>, <scene name='pdbsite=BC3:Mn+Binding+Site+For+Chain+C'>BC3</scene>, <scene name='pdbsite=BC4:Fbp+Binding+Site+For+Chain+D'>BC4</scene>, <scene name='pdbsite=BC5:Pga+Binding+Site+For+Chain+D'>BC5</scene>, <scene name='pdbsite=BC6:K+Binding+Site+For+Chain+D'>BC6</scene> and <scene name='pdbsite=BC7:Mn+Binding+Site+For+Chain+D'>BC7</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=FBP:FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=PGA:2-PHOSPHOGLYCOLIC+ACID'>PGA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene> and <scene name='pdbligand=MN:MANGANESE (II) ION'>MN</scene>
<table><tr><td colspan='2'>[[2vgb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1liu 1liu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VGB FirstGlance]. <br>
|ACTIVITY= [http://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.73&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PGA:2-PHOSPHOGLYCOLIC+ACID'>PGA</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=2vgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vgb OCA], [https://pdbe.org/2vgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vgb RCSB], [https://www.ebi.ac.uk/pdbsum/2vgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vgb ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Defects in PKLR are the cause of pyruvate kinase hyperactivity (PKHYP) [MIM:[https://omim.org/entry/102900 102900]; also known as high red cell ATP syndrome. This autosomal dominant phenotype is characterized by increase of red blood cell ATP.<ref>PMID:9090535</ref>   Defects in PKLR are the cause of pyruvate kinase deficiency of red cells (PKRD) [MIM:[https://omim.org/entry/266200 266200]. A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia.
== Function ==
[https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Plays a key role in glycolysis (By similarity).
== 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/vg/2vgb_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2vgb ConSurf].
<div style="clear:both"></div>


'''HUMAN ERYTHROCYTE PYRUVATE KINASE'''
==See Also==
 
*[[Pyruvate Kinase|Pyruvate Kinase]]
 
*[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]]
==Overview==
== References ==
Deficiency of human erythrocyte isozyme (RPK) is, together with glucose-6-phosphate dehydrogenase deficiency, the most common cause of the nonspherocytic hemolytic anemia. To provide a molecular framework to the disease, we have solved the 2.7 A resolution crystal structure of human RPK in complex with fructose 1,6-bisphosphate, the allosteric activator, and phosphoglycolate, a substrate analogue, and we have functionally and structurally characterized eight mutants (G332S, G364D, T384M, D390N, R479H, R486W, R504L, and R532W) found in RPK-deficient patients. The mutations target distinct regions of RPK structure, including domain interfaces and catalytic and allosteric sites. The mutations affect to a different extent thermostability, catalytic efficiency, and regulatory properties. These studies are the first to correlate the clinical symptoms with the molecular properties of the mutant enzymes. Mutations greatly impairing thermostability and/or activity are associated with severe anemia. Some mutant proteins exhibit moderate changes in the kinetic parameters, which are sufficient to cause mild to severe anemia, underlining the crucial role of RPK for erythrocyte metabolism. Prediction of the effects of mutations is difficult because there is no relation between the nature and location of the replaced amino acid and the type of molecular perturbation. Characterization of mutant proteins may serve as a valuable tool to assist with diagnosis and genetic counseling.
<references/>
 
__TOC__
==About this Structure==
</StructureSection>
2VGB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1LIU. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VGB OCA].
 
==Reference==
Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia., Valentini G, Chiarelli LR, Fortin R, Dolzan M, Galizzi A, Abraham DJ, Wang C, Bianchi P, Zanella A, Mattevi A, J Biol Chem. 2002 Jun 28;277(26):23807-14. Epub 2002 Apr 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11960989 11960989]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Pyruvate kinase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Abraham DJ]]
[[Category: Abraham, D J.]]
[[Category: Bianchi P]]
[[Category: Bianchi, P.]]
[[Category: Chiarelli L]]
[[Category: Chiarelli, L.]]
[[Category: Dolzan M]]
[[Category: Dolzan, M.]]
[[Category: Fortin R]]
[[Category: Fortin, R.]]
[[Category: Galizzi A]]
[[Category: Galizzi, A.]]
[[Category: Mattevi A]]
[[Category: Mattevi, A.]]
[[Category: Valentini G]]
[[Category: Valentini, G.]]
[[Category: Wang C]]
[[Category: Wang, C.]]
[[Category: Zanella A]]
[[Category: Zanella, A.]]
[[Category: FBP]]
[[Category: K]]
[[Category: MN]]
[[Category: PGA]]
[[Category: alternative splicing]]
[[Category: disease mutation]]
[[Category: glycolysis]]
[[Category: kinase]]
[[Category: magnesium]]
[[Category: metal-binding]]
[[Category: phosphorylation]]
[[Category: polymorphism]]
[[Category: pyruvate]]
[[Category: pyruvate kinase in the active r-state]]
[[Category: transferase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:46:18 2008''

Latest revision as of 10:07, 1 May 2024

HUMAN ERYTHROCYTE PYRUVATE KINASEHUMAN ERYTHROCYTE PYRUVATE KINASE

Structural highlights

2vgb is a 4 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1liu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.73Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KPYR_HUMAN Defects in PKLR are the cause of pyruvate kinase hyperactivity (PKHYP) [MIM:102900; also known as high red cell ATP syndrome. This autosomal dominant phenotype is characterized by increase of red blood cell ATP.[1] Defects in PKLR are the cause of pyruvate kinase deficiency of red cells (PKRD) [MIM:266200. A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia.

Function

KPYR_HUMAN Plays a key role in glycolysis (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Beutler E, Westwood B, van Zwieten R, Roos D. G-->T transition at cDNA nt 110 (K37Q) in the PKLR (pyruvate kinase) gene is the molecular basis of a case of hereditary increase of red blood cell ATP. Hum Mutat. 1997;9(3):282-5. PMID:9090535 doi:<282::AID-HUMU13>3.0.CO;2-Z 10.1002/(SICI)1098-1004(1997)9:3<282::AID-HUMU13>3.0.CO;2-Z

2vgb, resolution 2.73Å

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