4ajp: Difference between revisions

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-[[Image:4ajp.jpg|left|200px]]
-<!--
+==Human LDHA in complex with 2-((4-(4-((3-((2-methyl-1,3-benzothiazol- 6yl)amino)-3-oxo-propyl)amino)-4-oxo-butyl)phenyl)methyl)propanedioic acid==
-The line below this paragraph, containing "STRUCTURE_4ajp", creates the "Structure Box" on the page.
+<StructureSection load='4ajp' size='340' side='right'caption='[[4ajp]], [[Resolution|resolution]] 2.38&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'>[[4ajp]] is a 4 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=4AJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AJP 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]] 2.38&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=88N:{4-[4-({3-[(2-METHYL-1,3-BENZOTHIAZOL-6-YL)AMINO]-3-OXOPROPYL}AMINO)-4-OXOBUTYL]BENZYL}PROPANEDIOIC+ACID'>88N</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_4ajp|  PDB=4ajp  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ajp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ajp OCA], [https://pdbe.org/4ajp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ajp RCSB], [https://www.ebi.ac.uk/pdbsum/4ajp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ajp ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[https://omim.org/entry/612933 612933]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.
-===Human LDHA in complex with 2-((4-(4-((3-((2-methyl-1,3-benzothiazol- 6yl)amino)-3-oxo-propyl)amino)-4-oxo-butyl)phenyl)methyl)propanedioic acid===
+Design and synthesis of novel lactate dehydrogenase a inhibitors by fragment-based lead generation.,Ward RA, Brassington C, Breeze AL, Caputo A, Critchlow S, Davies G, Goodwin L, Hassall G, Greenwood R, Holdgate GA, Mrosek M, Norman RA, Pearson S, Tart J, Tucker JA, Vogtherr M, Whittaker D, Wingfield J, Winter J, Hudson K J Med Chem. 2012 Apr 12;55(7):3285-306. Epub 2012 Mar 26. PMID:22417091<ref>PMID:22417091</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4ajp" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[4ajp]] is a 4 chain structure with 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=4AJP OCA].
+*[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: L-lactate dehydrogenase]]
+[[Category: Large Structures]]
-[[Category: Brassington, C.]]
+[[Category: Brassington C]]
-[[Category: Caputo, A.]]
+[[Category: Caputo A]]
-[[Category: Davies, G.]]
+[[Category: Davies G]]
-[[Category: Pearson, S.]]
+[[Category: Pearson S]]
-[[Category: Tart, J.]]
+[[Category: Tart J]]
-[[Category: Tucker, J A.]]
+[[Category: Tucker JA]]
-[[Category: Ward, R.]]
+[[Category: Ward R]]
-[[Category: Watson, M.]]
+[[Category: Watson M]]
-[[Category: Fragment based lead generated inhibitor]]
-[[Category: Oxidoreductase-inhibitor complex]]