5ixy: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='5ixy' size='340' side='right'caption='[[5ixy]], [[Resolution|resolution]] 3.00Å' scene=''> | <StructureSection load='5ixy' size='340' side='right'caption='[[5ixy]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ixy]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5ixy]] 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=5IXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IXY FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GN2:(2~{S})-5-(2-CHLOROPHENYL)SULFANYL-2-(4-MORPHOLIN-4-YLPHENYL)-4-OXIDANYL-2-THIOPHEN-3-YL-1,3-DIHYDROPYRIDIN-6-ONE'>GN2</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GN2:(2~{S})-5-(2-CHLOROPHENYL)SULFANYL-2-(4-MORPHOLIN-4-YLPHENYL)-4-OXIDANYL-2-THIOPHEN-3-YL-1,3-DIHYDROPYRIDIN-6-ONE'>GN2</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5ixy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ixy OCA], [https://pdbe.org/5ixy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ixy RCSB], [https://www.ebi.ac.uk/pdbsum/5ixy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ixy ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 28: | Line 28: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chen | [[Category: Chen Z]] | ||
[[Category: Eigenbrot | [[Category: Eigenbrot C]] | ||
Latest revision as of 13:37, 6 September 2023
Lactate Dehydrogenase in complex with hydroxylactam inhibitor compound 31: (2~{S})-5-(2-chlorophenyl)sulfanyl-2-(4-morpholin-4-ylphenyl)-4-oxidanyl-2-thiophen-3-yl-1,3-dihydropyridin-6-oneLactate Dehydrogenase in complex with hydroxylactam inhibitor compound 31: (2~{S})-5-(2-chlorophenyl)sulfanyl-2-(4-morpholin-4-ylphenyl)-4-oxidanyl-2-thiophen-3-yl-1,3-dihydropyridin-6-one
Structural highlights
DiseaseLDHA_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] FunctionPublication Abstract from PubMedA series of trisubstituted hydroxylactams was identified as potent enzymatic and cellular inhibitors of human lactate dehydrogenase A. Utilizing structure-based design and physical property optimization, multiple inhibitors were discovered with <10 muM lactate IC50 in a MiaPaca2 cell line. Optimization of the series led to 29, a potent cell active molecule (MiaPaca2 IC50 = 0.67 muM) that also possessed good exposure when dosed orally to mice. Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice.,Purkey HE, Robarge K, Chen J, Chen Z, Corson LB, Ding CZ, DiPasquale AG, Dragovich PS, Eigenbrot C, Evangelista M, Fauber BP, Gao Z, Ge H, Hitz A, Ho Q, Labadie SS, Lai KW, Liu W, Liu Y, Li C, Ma S, Malek S, O'Brien T, Pang J, Peterson D, Salphati L, Sideris S, Ultsch M, Wei B, Yen I, Yue Q, Zhang H, Zhou A ACS Med Chem Lett. 2016 Aug 26;7(10):896-901. eCollection 2016 Oct 13. PMID:27774125[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||