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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Tzakos, A. G. | en |
| dc.contributor.author | Gerothanassis, I. P. | en |
| dc.date.accessioned | 2015-11-24T16:56:34Z | - |
| dc.date.available | 2015-11-24T16:56:34Z | - |
| dc.identifier.issn | 1439-4227 | - |
| dc.identifier.uri | https://olympias.lib.uoi.gr/jspui/handle/123456789/10454 | - |
| dc.rights | Default Licence | - |
| dc.subject | angiotensin i converting enzyme | en |
| dc.subject | drug design | en |
| dc.subject | inhibitors | en |
| dc.subject | metalloproteins | en |
| dc.subject | molecular modeling | en |
| dc.subject | molecular recognition | en |
| dc.subject | 2 active-sites | en |
| dc.subject | aspartyl-lysyl-proline | en |
| dc.subject | homologous domains | en |
| dc.subject | crystal-structure | en |
| dc.subject | protein models | en |
| dc.subject | kininase-ii | en |
| dc.subject | drug design | en |
| dc.subject | c-domain | en |
| dc.subject | peptide | en |
| dc.subject | substrate | en |
| dc.title | Domain-selective ligand-binding modes and atomic level pharmacophore refinement in angiotensin I converting enzyme (ACE) inhibitors | en |
| heal.type | journalArticle | - |
| heal.type.en | Journal article | en |
| heal.type.el | Άρθρο Περιοδικού | el |
| heal.identifier.primary | DOI 10.1002/cbic.200400386 | - |
| heal.identifier.secondary | <Go to ISI>://000229730000022 | - |
| heal.identifier.secondary | http://onlinelibrary.wiley.com/store/10.1002/cbic.200400386/asset/1089_ftp.pdf?v=1&t=hmn3j195&s=058c7a6aeb4696e93e6c7259dbd8414fed7d6e3a | - |
| heal.language | en | - |
| heal.access | campus | - |
| heal.recordProvider | Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας | el |
| heal.publicationDate | 2005 | - |
| heal.abstract | Somatic ACE (EC 3.4.15. 1), a Zn-II metalloproteinose, is composed of functionally active N and C domains resulting from tandem gene duplication. Despite the high degree of sequence similarity between the two domains, they differ in substrate and inhibitor specificity and in their activation by chloride ions. Because of the critical role of ACE in cardiovascular and renal diseases, both domains ore attractive targets for drug design. Putative structural models have been generated for the interactions of ACE inhibitors (lisinopril, captoril, enaloprilat, keto-ACE, ramiprilot, quinaprilat, peridoprilat, fosinoprilat, and RXP 407) with both the ACE-C and the ACE_N domains. Inhibitor-domain selectivity was interpreted in terms of residue alterations observed in the four subsites of the binding grooves of the ACE C/ACE N domains (SI: V516/N494, V578/T496, S2: F391/Y369, E403/R381, S1': D377/ Q355, E162/D140, V379/S357, V380/T358, and S2': D463/E431, T282/S260). The interactions governing the ligand-receptor recognition process in the ACE_C domain are: a salt bridge between D377, E162, and the NH2 group (P1' position), a hydrogen bond of the inhibitor with Q281, the presence of bulky hydrophobic groups in the P1 and P2' sites, and a stacking interaction of F391 with a benzyl group in the P2 position. In ACE_N these interactions are: hydrogen bonds of the inhibitor with E431, Y369, and R381, and a salt bridge between the carboxy group in the P2 position of the inhibitor and R500. The calculated complexes were evaluated for their consistency with structure-activity relationships and site-directed mutogenesis data. A comparison between the calculated interaction free energies and the experimentally observed biological activities was also made. Pharmocophore refinement was achieved at an atomic level, and might provide an improved basis for structure-based rational design of second-generation, domoin-selective inhibitors. | en |
| heal.publisher | Wiley-VCH Verlag | en |
| heal.journalName | Chembiochem | en |
| heal.journalType | peer reviewed | - |
| heal.fullTextAvailability | TRUE | - |
| Appears in Collections: | Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά). ΧΗΜ | |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Tzakos-2005-Domain-selective lig.pdf | 1.88 MB | Adobe PDF | View/Open Request a copy |
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