3mk6: Difference between revisions
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== | ==Substrate and Inhibitor Binding to Pank== | ||
[[http://www.uniprot.org/uniprot/PANK3_HUMAN PANK3_HUMAN | <StructureSection load='3mk6' size='340' side='right'caption='[[3mk6]], [[Resolution|resolution]] 1.98Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3mk6]] 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=3MK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MK6 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]] 1.98Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=3mk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mk6 OCA], [https://pdbe.org/3mk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mk6 RCSB], [https://www.ebi.ac.uk/pdbsum/3mk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mk6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PANK3_HUMAN PANK3_HUMAN] Plays a role in the physiological regulation of the intracellular CoA concentration (By similarity). | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mk/3mk6_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3mk6 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis of site-directed mutants indicates that pantothenate binds in a tunnel adjacent to the active site that is occupied by the pantothenate moiety of the acetyl-CoA regulator in the PanK3acetyl-CoA binary complex. A high-throughput screen for PanK3 inhibitors and activators was applied to a bioactive compound library. Thiazolidinediones, sulfonylureas and steroids were inhibitors, and fatty acyl-amides and tamoxifen were activators. The PanK3 activators and inhibitors either stimulated or repressed CoA biosynthesis in HepG2/C3A cells. The flexible allosteric acetyl-CoA regulatory domain of PanK3 also binds the substrates, pantothenate and pantetheine, and small molecule inhibitors and activators to modulate PanK3 activity. | |||
Modulation of pantothenate kinase 3 activity by small molecules that interact with the substrate/allosteric regulatory domain.,Leonardi R, Zhang YM, Yun MK, Zhou R, Zeng FY, Lin W, Cui J, Chen T, Rock CO, White SW, Jackowski S Chem Biol. 2010 Aug 27;17(8):892-902. PMID:20797618<ref>PMID:20797618</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3mk6" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Pantothenate kinase|Pantothenate kinase]] | *[[Pantothenate kinase 3D structures|Pantothenate kinase 3D structures]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: White | [[Category: White SW]] | ||
[[Category: Yun | [[Category: Yun M-K]] | ||
Latest revision as of 11:55, 6 September 2023
Substrate and Inhibitor Binding to PankSubstrate and Inhibitor Binding to Pank
Structural highlights
FunctionPANK3_HUMAN Plays a role in the physiological regulation of the intracellular CoA concentration (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis of site-directed mutants indicates that pantothenate binds in a tunnel adjacent to the active site that is occupied by the pantothenate moiety of the acetyl-CoA regulator in the PanK3acetyl-CoA binary complex. A high-throughput screen for PanK3 inhibitors and activators was applied to a bioactive compound library. Thiazolidinediones, sulfonylureas and steroids were inhibitors, and fatty acyl-amides and tamoxifen were activators. The PanK3 activators and inhibitors either stimulated or repressed CoA biosynthesis in HepG2/C3A cells. The flexible allosteric acetyl-CoA regulatory domain of PanK3 also binds the substrates, pantothenate and pantetheine, and small molecule inhibitors and activators to modulate PanK3 activity. Modulation of pantothenate kinase 3 activity by small molecules that interact with the substrate/allosteric regulatory domain.,Leonardi R, Zhang YM, Yun MK, Zhou R, Zeng FY, Lin W, Cui J, Chen T, Rock CO, White SW, Jackowski S Chem Biol. 2010 Aug 27;17(8):892-902. PMID:20797618[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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