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==X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7)== | ==X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7)== | ||
<StructureSection load='6sbv' size='340' side='right'caption='[[6sbv]]' scene=''> | <StructureSection load='6sbv' size='340' side='right'caption='[[6sbv]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SBV OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6sbv]] is a 8 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=6SBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SBV FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L5K:~{N}-[3-[(7-nitrodibenzofuran-2-yl)sulfonylamino]phenyl]-1-oxidanyl-cyclopropane-1-carboxamide'>L5K</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=6sbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sbv OCA], [https://pdbe.org/6sbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sbv RCSB], [https://www.ebi.ac.uk/pdbsum/6sbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sbv ProSAT]</span></td></tr> | |||
</table> | </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) is frequently overexpressed in tumors, thereby sustaining high glycolysis rates, tumor growth, and chemoresistance. High-throughput screening resulted in the identification of phthalimide and dibenzofuran derivatives as novel lactate dehydrogenase inhibitors, selectively inhibiting the activity of the LDHA isoenzyme. Cocrystallization experiments confirmed target engagement in addition to demonstrating binding to a novel allosteric binding site present in all four LDHA subunits of the LDH5 homotetramer. | |||
Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A.,Friberg A, Rehwinkel H, Nguyen D, Putter V, Quanz M, Weiske J, Eberspacher U, Heisler I, Langer G ACS Omega. 2020 May 27;5(22):13034-13041. doi: 10.1021/acsomega.0c00715., eCollection 2020 Jun 9. PMID:32548488<ref>PMID:32548488</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6sbv" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Friberg A]] | [[Category: Friberg A]] | ||
Latest revision as of 15:39, 24 January 2024
X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7)X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7)
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 PubMedLactate dehydrogenase A (LDHA) is frequently overexpressed in tumors, thereby sustaining high glycolysis rates, tumor growth, and chemoresistance. High-throughput screening resulted in the identification of phthalimide and dibenzofuran derivatives as novel lactate dehydrogenase inhibitors, selectively inhibiting the activity of the LDHA isoenzyme. Cocrystallization experiments confirmed target engagement in addition to demonstrating binding to a novel allosteric binding site present in all four LDHA subunits of the LDH5 homotetramer. Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A.,Friberg A, Rehwinkel H, Nguyen D, Putter V, Quanz M, Weiske J, Eberspacher U, Heisler I, Langer G ACS Omega. 2020 May 27;5(22):13034-13041. doi: 10.1021/acsomega.0c00715., eCollection 2020 Jun 9. PMID:32548488[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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