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==Crystal structure of human glucose transporter GLUT3 bound with exofacial inhibitor SA47== | ==Crystal structure of human glucose transporter GLUT3 bound with exofacial inhibitor SA47== | ||
<StructureSection load='7sps' size='340' side='right'caption='[[7sps]]' scene=''> | <StructureSection load='7sps' size='340' side='right'caption='[[7sps]], [[Resolution|resolution]] 2.30Å' 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=7SPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SPS FirstGlance]. <br> | <table><tr><td colspan='2'>[[7sps]] is a 2 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=7SPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SPS FirstGlance]. <br> | ||
</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=7sps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sps OCA], [https://pdbe.org/7sps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sps RCSB], [https://www.ebi.ac.uk/pdbsum/7sps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sps ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A0E:methyl+N-[(2-{4-[4-(5-fluoro-2-methoxyphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl}phenyl)methyl]-beta-alaninate'>A0E</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</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=7sps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sps OCA], [https://pdbe.org/7sps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sps RCSB], [https://www.ebi.ac.uk/pdbsum/7sps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sps ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/GTR3_HUMAN GTR3_HUMAN] Huntington disease. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GTR3_HUMAN GTR3_HUMAN] Facilitative glucose transporter. Probably a neuronal glucose transporter. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human glucose transporters (GLUTs) are responsible for cellular uptake of hexoses. Elevated expression of GLUTs, particularly GLUT1 and GLUT3, is required to fuel the hyperproliferation of cancer cells, making GLUT inhibitors potential anticancer therapeutics. Meanwhile, GLUT inhibitor-conjugated insulin is being explored to mitigate the hypoglycemia side effect of insulin therapy in type 1 diabetes. Reasoning that exofacial inhibitors of GLUT1/3 may be favored for therapeutic applications, we report here the engineering of a GLUT3 variant, designated GLUT3exo, that can be probed for screening and validating exofacial inhibitors. We identify an exofacial GLUT3 inhibitor SA47 and elucidate its mode of action by a 2.3 A resolution crystal structure of SA47-bound GLUT3. Our studies serve as a framework for the discovery of GLUTs exofacial inhibitors for therapeutic development. | |||
Molecular basis for inhibiting human glucose transporters by exofacial inhibitors.,Wang N, Zhang S, Yuan Y, Xu H, Defossa E, Matter H, Besenius M, Derdau V, Dreyer M, Halland N, He KH, Petry S, Podeschwa M, Tennagels N, Jiang X, Yan N Nat Commun. 2022 May 12;13(1):2632. doi: 10.1038/s41467-022-30326-3. PMID:35552392<ref>PMID:35552392</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7sps" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Jiang X]] | [[Category: Jiang X]] | ||
[[Category: Wang N]] | [[Category: Wang N]] | ||
[[Category: Yan N]] | [[Category: Yan N]] | ||
Latest revision as of 19:54, 18 October 2023
Crystal structure of human glucose transporter GLUT3 bound with exofacial inhibitor SA47Crystal structure of human glucose transporter GLUT3 bound with exofacial inhibitor SA47
Structural highlights
DiseaseGTR3_HUMAN Huntington disease. FunctionGTR3_HUMAN Facilitative glucose transporter. Probably a neuronal glucose transporter. Publication Abstract from PubMedHuman glucose transporters (GLUTs) are responsible for cellular uptake of hexoses. Elevated expression of GLUTs, particularly GLUT1 and GLUT3, is required to fuel the hyperproliferation of cancer cells, making GLUT inhibitors potential anticancer therapeutics. Meanwhile, GLUT inhibitor-conjugated insulin is being explored to mitigate the hypoglycemia side effect of insulin therapy in type 1 diabetes. Reasoning that exofacial inhibitors of GLUT1/3 may be favored for therapeutic applications, we report here the engineering of a GLUT3 variant, designated GLUT3exo, that can be probed for screening and validating exofacial inhibitors. We identify an exofacial GLUT3 inhibitor SA47 and elucidate its mode of action by a 2.3 A resolution crystal structure of SA47-bound GLUT3. Our studies serve as a framework for the discovery of GLUTs exofacial inhibitors for therapeutic development. Molecular basis for inhibiting human glucose transporters by exofacial inhibitors.,Wang N, Zhang S, Yuan Y, Xu H, Defossa E, Matter H, Besenius M, Derdau V, Dreyer M, Halland N, He KH, Petry S, Podeschwa M, Tennagels N, Jiang X, Yan N Nat Commun. 2022 May 12;13(1):2632. doi: 10.1038/s41467-022-30326-3. PMID:35552392[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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