4r68
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4r68 is ON HOLD Authors: Eigenbrot, C., Ultsch, M. Description: Lactate Dehydrogenase in complex with inhibitor compound 31) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Lactate Dehydrogenase in complex with inhibitor compound 31== | |
| + | <StructureSection load='4r68' size='340' side='right'caption='[[4r68]], [[Resolution|resolution]] 2.11Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4r68]] 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=4R68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R68 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]] 2.112Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=W31:(1S)-1-PHENYLETHYL+(4-CHLORO-3-{[(4S)-4-(2,6-DICHLOROPHENYL)-2-HYDROXY-6-OXOCYCLOHEX-1-EN-1-YL]SULFANYL}PHENYL)ACETATE'>W31</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=4r68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r68 OCA], [https://pdbe.org/4r68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r68 RCSB], [https://www.ebi.ac.uk/pdbsum/4r68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r68 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 == | ||
| + | Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enone using structure-based design strategies resulted in inhibitors with considerable improvement in biochemical potency against human lactate dehydrogenase A (LDHA). These potent inhibitors were typically selective for LDHA over LDHB isoform (4-10 fold) and other structurally related malate dehydrogenases, MDH1 and MDH2 (>500 fold). An X-ray crystal structure of enzymatically most potent molecule bound to LDHA revealed two additional interactions associated with enhanced biochemical potency. | ||
| - | + | Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase.,Labadie S, Dragovich PS, Chen J, Fauber BP, Boggs J, Corson LB, Ding CZ, Eigenbrot C, Ge H, Ho Q, Lai KW, Ma S, Malek S, Peterson D, Purkey HE, Robarge K, Salphati L, Sideris S, Ultsch M, VanderPorten E, Wei B, Xu Q, Yen I, Yue Q, Zhang H, Zhang X, Zhou A Bioorg Med Chem Lett. 2014 Nov 10;25(1):75-82. doi: 10.1016/j.bmcl.2014.11.008. PMID:25466195<ref>PMID:25466195</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4r68" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Eigenbrot C]] | ||
| + | [[Category: Ultsch M]] | ||
Current revision
Lactate Dehydrogenase in complex with inhibitor compound 31
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