5scf: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 3: / Line 3: @@
 <StructureSection load='5scf' size='340' side='right'caption='[[5scf]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5scf]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SCF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5scf]] is a 8 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=5SCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SCF FirstGlance]. <br>
-</td></tr><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=I91:N-(3-hydroxy-9,10-dioxo-9,10-dihydroanthracene-2-sulfonyl)glycine'>I91</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</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]] 2.185&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </span></td></tr>
+<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=I91:N-(3-hydroxy-9,10-dioxo-9,10-dihydroanthracene-2-sulfonyl)glycine'>I91</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</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=5scf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5scf OCA], [https://pdbe.org/5scf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5scf RCSB], [https://www.ebi.ac.uk/pdbsum/5scf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5scf ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Disease ==
-== Publication Abstract from PubMed ==
+[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.
-Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP production during liver cell glycolysis and is considered a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). In this study, we report the first ADP-competitive PKL inhibitors and identify several starting points for the further optimization of these inhibitors. Modeling and structural biology guided the optimization of a PKL-specific anthraquinone-based compound. A structure-activity relationship study of 47 novel synthetic derivatives revealed PKL inhibitors with half-maximal inhibitory concentration (IC50) values in the 200 nM range. Despite the difficulty involved in studying a binding site as exposed as the ADP site, these derivatives feature expanded structural diversity and chemical spaces that may be used to improve their inhibitory activities against PKL. The obtained results expand the knowledge of the structural requirements for interactions with the ADP-binding site of PKL.
+== Function ==
+[https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Plays a key role in glycolysis (By similarity).
-Anthraquinone derivatives as ADP-competitive inhibitors of liver pyruvate kinase.,Nain-Perez A, Foller Fuchtbauer A, Haversen L, Lulla A, Gao C, Matic J, Monjas L, Rodriguez A, Brear P, Kim W, Hyvonen M, Boren J, Mardinoglu A, Uhlen M, Grotli M Eur J Med Chem. 2022 Mar 8;234:114270. doi: 10.1016/j.ejmech.2022.114270. PMID:35290845<ref>PMID:35290845</ref>
+==See Also==
+*[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 5scf" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Pyruvate kinase]]
+[[Category: Brear P]]
-[[Category: Brear, P]]
+[[Category: Foller A]]
-[[Category: Foller, A]]
+[[Category: Grotli M]]
-[[Category: Grotli, M]]
+[[Category: Hyvonen M]]
-[[Category: Hyvonen, M]]
+[[Category: Lulla A]]
-[[Category: Lulla, A]]
+[[Category: Nain-Perez A]]
-[[Category: Nain-Perez, A]]
-[[Category: Active site]]
-[[Category: Inhibition]]
-[[Category: Transferase]]
-[[Category: Transferase-transferase inhibitor complex]]