4m49: Difference between revisions

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-{{STRUCTURE_4m49|  PDB=4m49  |  SCENE=  }}
+==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]] 2.05&Aring;' scene=''>
-{{ABSTRACT_PUBMED_24012183}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4m49]] 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=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>
+<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 Homo sapiens])</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>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN]] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[http://omim.org/entry/612933 612933]]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref>
+== Function ==
-==Disease==
+<div style="background-color:#fffaf0;">
-[[http://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN]] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[http://omim.org/entry/612933 612933]]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref>
+== Publication Abstract from PubMed ==
+A 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<ref>PMID:24012183</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4m49]] 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=4M49 OCA].
+</div>
-==Reference==
+==See Also==
-<ref group="xtra">PMID:024012183</ref><references group="xtra"/><references/>
+*[[Lactate Dehydrogenase|Lactate Dehydrogenase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: L-lactate dehydrogenase]]
-[[Category: Eigenbrot, C.]]
+[[Category: Eigenbrot, C]]
-[[Category: Ultsch, M.]]
+[[Category: Ultsch, M]]
 [[Category: Dehydrogenase/reductase]]
 [[Category: Nicotinamide adenine dinucleotide nadh]]
 [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]