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==Crystal Structure of Human Hexokinase 2 with cmpd 30, a 2-amino-6-benzenesulfonamide glucosamine== | |||
<StructureSection load='5hex' size='340' side='right' caption='[[5hex]], [[Resolution|resolution]] 2.73Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5hex]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HEX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HEX FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=604:5-[[(2~{R},3~{S},4~{R},5~{R},6~{S})-5-[(3-BROMOPHENYL)CARBONYLAMINO]-3,4,6-TRIS(OXIDANYL)OXAN-2-YL]METHYLSULFAMOYL]-2-METHYL-FURAN-3-CARBOXYLIC+ACID'>604</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hfu|5hfu]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hexokinase Hexokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.1 2.7.1.1] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hex OCA], [http://pdbe.org/5hex PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hex RCSB], [http://www.ebi.ac.uk/pdbsum/5hex PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A novel series of potent and selective hexokinase 2 (HK2) inhibitors, 2,6-disubstituted glucosamines, has been identified based on HTS hits, exemplified by compound 1. Inhibitor-bound crystal structures revealed that the HK2 enzyme could adopt an "induced-fit" conformation. The SAR study led to the identification of potent HK2 inhibitors, such as compound 34 with greater than 100-fold selectivity over HK1. Compound 25 inhibits in situ glycolysis in a UM-UC-3 bladder tumor cell line via (13)CNMR measurement of [3-(13)C]lactate produced from [1,6-(13)C2]glucose added to the cell culture. | |||
Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors.,Lin H, Zeng J, Xie R, Schulz MJ, Tedesco R, Qu J, Erhard KF, Mack JF, Raha K, Rendina AR, Szewczuk LM, Kratz PM, Jurewicz AJ, Cecconie T, Martens S, McDevitt PJ, Martin JD, Chen SB, Jiang Y, Nickels L, Schwartz BJ, Smallwood A, Zhao B, Campobasso N, Qian Y, Briand J, Rominger CM, Oleykowski C, Hardwicke MA, Luengo JI ACS Med Chem Lett. 2015 Dec 28;7(3):217-22. doi: 10.1021/acsmedchemlett.5b00214. , eCollection 2016 Mar 10. PMID:26985301<ref>PMID:26985301</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5hex" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hexokinase]] | |||
[[Category: Campobasso, N]] | |||
[[Category: Smallwood, A]] | [[Category: Smallwood, A]] | ||
[[Category: Zhao, B]] | [[Category: Zhao, B]] | ||
[[Category: | [[Category: Inhibitor complex]] | ||
[[Category: Transferase-transferase inhibitor complex]] | |||
Revision as of 23:36, 11 May 2016
Crystal Structure of Human Hexokinase 2 with cmpd 30, a 2-amino-6-benzenesulfonamide glucosamineCrystal Structure of Human Hexokinase 2 with cmpd 30, a 2-amino-6-benzenesulfonamide glucosamine
Structural highlights
Publication Abstract from PubMedA novel series of potent and selective hexokinase 2 (HK2) inhibitors, 2,6-disubstituted glucosamines, has been identified based on HTS hits, exemplified by compound 1. Inhibitor-bound crystal structures revealed that the HK2 enzyme could adopt an "induced-fit" conformation. The SAR study led to the identification of potent HK2 inhibitors, such as compound 34 with greater than 100-fold selectivity over HK1. Compound 25 inhibits in situ glycolysis in a UM-UC-3 bladder tumor cell line via (13)CNMR measurement of [3-(13)C]lactate produced from [1,6-(13)C2]glucose added to the cell culture. Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors.,Lin H, Zeng J, Xie R, Schulz MJ, Tedesco R, Qu J, Erhard KF, Mack JF, Raha K, Rendina AR, Szewczuk LM, Kratz PM, Jurewicz AJ, Cecconie T, Martens S, McDevitt PJ, Martin JD, Chen SB, Jiang Y, Nickels L, Schwartz BJ, Smallwood A, Zhao B, Campobasso N, Qian Y, Briand J, Rominger CM, Oleykowski C, Hardwicke MA, Luengo JI ACS Med Chem Lett. 2015 Dec 28;7(3):217-22. doi: 10.1021/acsmedchemlett.5b00214. , eCollection 2016 Mar 10. PMID:26985301[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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