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==Structure of a beta galactosidase with inhibitor== | ==Structure of a beta galactosidase with inhibitor== | ||
<StructureSection load='6tbk' size='340' side='right'caption='[[6tbk]]' scene=''> | <StructureSection load='6tbk' size='340' side='right'caption='[[6tbk]], [[Resolution|resolution]] 1.60Å' 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=6TBK OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6tbk]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Cellvibrio_japonicus_Ueda107 Cellvibrio japonicus Ueda107]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TBK 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]] 1.6Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N0Q:5-(dimethylamino)-~{N}-[6-[(2~{R},3~{R},4~{S},5~{R})-3-(hydroxymethyl)-4,5-bis(oxidanyl)piperidin-2-yl]hexyl]naphthalene-1-sulfonamide'>N0Q</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=6tbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tbk OCA], [https://pdbe.org/6tbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tbk RCSB], [https://www.ebi.ac.uk/pdbsum/6tbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tbk ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/B3PBE0_CELJU B3PBE0_CELJU] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Glycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series of new cyclopentanoid beta-galactosidase inhibitors were prepared and their inhibitory and pharmacological chaperoning activities determined and compared with those of lipophilic analogs of the potent beta-d-galactosidase inhibitor 4-epi-isofagomine. Structure-activity relationships were investigated by X-ray crystallography as well as by alterations in the cyclopentane moiety such as deoxygenation and replacement by fluorine of a "strategic" hydroxyl group. New compounds have revealed highly promising activities with a range of beta-galactosidase-compromised human cell lines and may serve as leads towards new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease. | |||
Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity: Highly Functionalized Aminocyclopentanes and C-5a-Substituted Derivatives of 4-epi-Isofagomine.,Weber P, Thonhofer M, Averill S, Davies GJ, Santana AG, Muller P, Nasseri SA, Offen WA, Pabst BM, Paschke E, Schalli M, Torvisco A, Tschernutter M, Tysoe C, Windischhofer W, Withers SG, Wolfsgruber A, Wrodnigg TM, Stutz AE Molecules. 2020 Sep 3;25(17). pii: molecules25174025. doi:, 10.3390/molecules25174025. PMID:32899288<ref>PMID:32899288</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6tbk" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Galactosidase 3D structures|Galactosidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Cellvibrio japonicus Ueda107]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Davies G]] | [[Category: Davies G]] | ||
[[Category: Offen W]] | [[Category: Offen W]] | ||
Latest revision as of 15:59, 24 January 2024
Structure of a beta galactosidase with inhibitorStructure of a beta galactosidase with inhibitor
Structural highlights
FunctionPublication Abstract from PubMedGlycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series of new cyclopentanoid beta-galactosidase inhibitors were prepared and their inhibitory and pharmacological chaperoning activities determined and compared with those of lipophilic analogs of the potent beta-d-galactosidase inhibitor 4-epi-isofagomine. Structure-activity relationships were investigated by X-ray crystallography as well as by alterations in the cyclopentane moiety such as deoxygenation and replacement by fluorine of a "strategic" hydroxyl group. New compounds have revealed highly promising activities with a range of beta-galactosidase-compromised human cell lines and may serve as leads towards new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease. Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity: Highly Functionalized Aminocyclopentanes and C-5a-Substituted Derivatives of 4-epi-Isofagomine.,Weber P, Thonhofer M, Averill S, Davies GJ, Santana AG, Muller P, Nasseri SA, Offen WA, Pabst BM, Paschke E, Schalli M, Torvisco A, Tschernutter M, Tysoe C, Windischhofer W, Withers SG, Wolfsgruber A, Wrodnigg TM, Stutz AE Molecules. 2020 Sep 3;25(17). pii: molecules25174025. doi:, 10.3390/molecules25174025. PMID:32899288[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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