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==Lactate Dehydrogenase A in complex with a substituted pyrazine inhibitor compound 18== | ==Lactate Dehydrogenase A in complex with a substituted pyrazine inhibitor compound 18== | ||
<StructureSection load='4m49' size='340' side='right' caption='[[4m49]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='4m49' size='340' side='right' caption='[[4m49]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4m49]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4m49]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M49 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M49 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=22Y:3-(5-AMINO-6-{[(1R)-1-PHENYLETHYL]AMINO}PYRAZIN-2-YL)-4-CHLOROBENZOIC+ACID'>22Y</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=LAC:LACTIC+ACID'>LAC</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=22Y:3-(5-AMINO-6-{[(1R)-1-PHENYLETHYL]AMINO}PYRAZIN-2-YL)-4-CHLOROBENZOIC+ACID'>22Y</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=LAC:LACTIC+ACID'>LAC</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jnk|4jnk]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jnk|4jnk]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LDHA, PIG19 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LDHA, PIG19 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m49 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m49 RCSB], [http://www.ebi.ac.uk/pdbsum/4m49 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m49 OCA], [http://pdbe.org/4m49 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m49 RCSB], [http://www.ebi.ac.uk/pdbsum/4m49 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m49 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4m49" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: L-lactate dehydrogenase]] | [[Category: L-lactate dehydrogenase]] | ||
[[Category: Eigenbrot, C]] | [[Category: Eigenbrot, C]] | ||
Revision as of 01:00, 6 August 2016
Lactate Dehydrogenase A in complex with a substituted pyrazine inhibitor compound 18Lactate Dehydrogenase A in complex with a substituted pyrazine inhibitor compound 18
Structural highlights
Disease[LDHA_HUMAN] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:612933]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.[1] Publication Abstract from PubMedA 2-amino-5-aryl-pyrazine was identified as an inhibitor of human lactate dehydrogenase A (LDHA) via a biochemical screening campaign. Biochemical and biophysical experiments demonstrated that the compound specifically interacted with human LDHA. Structural variation of the screening hit resulted in improvements in LDHA biochemical inhibition and pharmacokinetic properties. A crystal structure of an improved compound bound to human LDHA was also obtained and it explained many of the observed structure-activity relationships. Identification of 2-amino-5-aryl-pyrazines as inhibitors of human lactate dehydrogenase.,Fauber BP, Dragovich PS, Chen J, Corson LB, Ding CZ, Eigenbrot C, Giannetti AM, Hunsaker T, Labadie S, Liu Y, Liu Y, Malek S, Peterson D, Pitts K, Sideris S, Ultsch M, Vanderporten E, Wang J, Wei B, Yen I, Yue Q Bioorg Med Chem Lett. 2013 Oct 15;23(20):5533-9. doi: 10.1016/j.bmcl.2013.08.060., Epub 2013 Aug 22. PMID:24012183[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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