dc.contributor.author | Oikonomakos, Nikos G. | en |
dc.contributor.author | Zographos, Spyros E. | en |
dc.contributor.author | Skamnaki, Vicky T. | en |
dc.contributor.author | Archontis, Georgios Z. | en |
dc.creator | Oikonomakos, Nikos G. | en |
dc.creator | Zographos, Spyros E. | en |
dc.creator | Skamnaki, Vicky T. | en |
dc.creator | Archontis, Georgios Z. | en |
dc.date.accessioned | 2019-12-02T15:32:05Z | |
dc.date.available | 2019-12-02T15:32:05Z | |
dc.date.issued | 2002 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/58916 | |
dc.description.abstract | CP320626, a potential antidiabetic drug, inhibits glycogen phosphorylase in synergism with glucose. To elucidate the structural basis of synergistic inhibition, we determined the structure of muscle glycogen phosphorylase b (MGPb) complexed with both glucose and CP320626 at 1.76 Å resolution, and refined to a crystallographic R value of 0.211 (Rfree = 0.235). CP320626 binds at a novel allosteric site, which is some 33 Å from the catalytic site, where glucose binds. The high resolution structure allows unambiguous definition of the conformation of the 1-acetyl-4-hydroxy-piperidine ring supported by theoretical energy calculations. Both CP320626 and glucose promote the less active T-state, thereby explaining their synergistic inhibition. Structural comparison of MGPb-glucose-CP320626 complex with liver glycogen phosphorylase a (LGPa) complexed with a related compound (CP403700) show that the ligand binding site is conserved in LGPa. © 2002 Elsevier Science Ltd. All rights reserved. | en |
dc.source | Bioorganic and Medicinal Chemistry | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0036185751&doi=10.1016%2fS0968-0896%2801%2900394-7&partnerID=40&md5=faeb94013f67e5299fb6e7bd5a6908a4 | |
dc.subject | article | en |
dc.subject | human | en |
dc.subject | Humans | en |
dc.subject | unclassified drug | en |
dc.subject | drug potentiation | en |
dc.subject | metabolism | en |
dc.subject | glucose | en |
dc.subject | Indoles | en |
dc.subject | Enzyme Inhibitors | en |
dc.subject | chemistry | en |
dc.subject | Drug Synergism | en |
dc.subject | protein binding | en |
dc.subject | enzyme inhibition | en |
dc.subject | crystal structure | en |
dc.subject | structure analysis | en |
dc.subject | chemical structure | en |
dc.subject | X ray crystallography | en |
dc.subject | calculation | en |
dc.subject | indole derivative | en |
dc.subject | protein conformation | en |
dc.subject | drug binding | en |
dc.subject | Molecular Structure | en |
dc.subject | structure activity relation | en |
dc.subject | binding site | en |
dc.subject | enzyme active site | en |
dc.subject | drug protein binding | en |
dc.subject | Models, Molecular | en |
dc.subject | drug structure | en |
dc.subject | Crystallography, X-Ray | en |
dc.subject | enzyme structure | en |
dc.subject | Amides | en |
dc.subject | antidiabetic agent | en |
dc.subject | Hypoglycemic Agents | en |
dc.subject | amide | en |
dc.subject | piperidine derivative | en |
dc.subject | Catalytic Domain | en |
dc.subject | allosterism | en |
dc.subject | enzyme inhibitor | en |
dc.subject | drug conformation | en |
dc.subject | 1 acetyl 4 hydroxypiperidine | en |
dc.subject | 5 chloro 1h indole 2 carboxylic acid [1 (fluorobenzyl) 2 (4 hydroxypiperidin 1 yl) 2 oxoethyl]amide | en |
dc.subject | Allosteric Site | en |
dc.subject | CP 320626 | en |
dc.subject | cp 403700 | en |
dc.subject | cp320626 | en |
dc.subject | cp403700 | en |
dc.subject | glycogen phosphorylase | en |
dc.subject | glycogen phosphorylase b | en |
dc.subject | Glycogen Phosphorylase, Muscle Form | en |
dc.subject | muscle enzyme | en |
dc.title | The 1.76 Å resolution crystal structure of glycogen phosphorylase b complexed with glucose, and CP320626, a potential antidiabetic drug | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1016/S0968-0896(01)00394-7 | |
dc.description.volume | 10 | |
dc.description.issue | 5 | |
dc.description.startingpage | 1313 | |
dc.description.endingpage | 1319 | |
dc.author.faculty | Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Φυσικής / Department of Physics | |
dc.type.uhtype | Article | en |
dc.description.notes | <p>Tradenames: cp 403700 | en |
dc.description.notes | cp320626 | en |
dc.description.notes | Cited By :26</p> | en |
dc.source.abbreviation | Bioorg.Med.Chem. | en |
dc.contributor.orcid | Zographos, Spyros E. [0000-0001-8455-2352] | |
dc.contributor.orcid | Archontis, Georgios Z. [0000-0002-7750-8641] | |
dc.gnosis.orcid | 0000-0001-8455-2352 | |
dc.gnosis.orcid | 0000-0002-7750-8641 | |