3c3c: Difference between revisions

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-{{Seed}}
-[[Image:3c3c.png|left|200px]]
-<!--
+==Crystal Structure of human phosphoglycerate kinase bound to 3-phosphoglycerate and L-CDP==
-The line below this paragraph, containing "STRUCTURE_3c3c", creates the "Structure Box" on the page.
+<StructureSection load='3c3c' size='340' side='right'caption='[[3c3c]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3c3c]] is a 2 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=3C3C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C3C FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#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=CDP:CYTIDINE-5-DIPHOSPHATE'>CDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-{{STRUCTURE_3c3c|  PDB=3c3c  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c3c OCA], [https://pdbe.org/3c3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c3c RCSB], [https://www.ebi.ac.uk/pdbsum/3c3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c3c 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/c3/3c3c_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=3c3c ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Non-natural L-nucleoside analogues are increasingly used as therapeutic agents to treat cancer and viral infections. To be active, L-nucleosides need to be phosphorylated to their respective triphosphate metabolites. This stepwise phosphorylation relies on human enzymes capable of processing L-nucleoside enantiomers. We used crystallographic analysis to reveal the molecular basis for the low enantioselectivity and the broad specificity of human 3-phosphoglycerate kinase (hPGK), an enzyme responsible for the last step of phosphorylation of many nucleotide derivatives. Based on structures of hPGK in the absence of nucleotides, and bound to L and d forms of MgADP and MgCDP, we show that a non-specific hydrophobic clamp to the nucleotide base, as well as a water-filled cavity behind it, allows high flexibility in the interaction between PGK and the bases. This, combined with the dispensability of hydrogen bonds to the sugar moiety, and ionic interactions with the phosphate groups, results in the positioning of different nucleotides so to expose their diphosphate group in a position competent for catalysis. Since the third phosphorylation step is often rate limiting, our results are expected to alleviate in silico tailoring of L-type prodrugs to assure their efficient metabolic processing.
-===Crystal Structure of human phosphoglycerate kinase bound to 3-phosphoglycerate and L-CDP===
+Molecular basis for the lack of enantioselectivity of human 3-phosphoglycerate kinase.,Gondeau C, Chaloin L, Lallemand P, Roy B, Perigaud C, Barman T, Varga A, Vas M, Lionne C, Arold ST Nucleic Acids Res. 2008 Jun;36(11):3620-9. Epub 2008 May 7. PMID:18463139<ref>PMID:18463139</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3c3c" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_18463139}}, adds the Publication Abstract to the page
+*[[Phosphoglycerate kinase 3D structures|Phosphoglycerate kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 18463139 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_18463139}}
+__TOC__
+</StructureSection>
-==Disease==
-Known disease associated with this structure: Phosphoglycerate kinase 1 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=311800 311800]]
-==About this Structure==
-C3C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C3C OCA].
-==Reference==
-Molecular basis for the lack of enantioselectivity of human 3-phosphoglycerate kinase., Gondeau C, Chaloin L, Lallemand P, Roy B, Perigaud C, Barman T, Varga A, Vas M, Lionne C, Arold ST, Nucleic Acids Res. 2008 Jun;36(11):3620-9. Epub 2008 May 7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18463139 18463139]
 [[Category: Homo sapiens]]
-[[Category: Phosphoglycerate kinase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Arold ST]]
-[[Category: Arold, S T.]]
+[[Category: Chaloin L]]
-[[Category: Chaloin, L.]]
+[[Category: Gondeau C]]
-[[Category: Gondeau, C.]]
+[[Category: Lionne C]]
-[[Category: Lionne, C.]]
-[[Category: Acetylation]]
-[[Category: Atp-binding]]
-[[Category: Cytoplasm]]
-[[Category: Disease mutation]]
-[[Category: Glycolysis]]
-[[Category: Hereditary hemolytic anemia]]
-[[Category: Kinase]]
-[[Category: L-enantiomer of cdp]]
-[[Category: Nucleotide-binding]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism]]
-[[Category: Protein-nucleotide complex]]
-[[Category: Transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:21:18 2008''