Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II \"selective\" inhibitor celecoxib. (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II \"selective\" inhibitor celecoxib. (Articolo in rivista) (literal)

Anno

• 2006-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1016/j.bmcl.2005.09.040 (literal)

Alternative label

• Di Fiore, Anna; Pedone, Carlo; D'Ambrosio, Katia; Scozzafava, Andrea; De Simone, Giuseppina; Supuran, Claudiu T. (2006)
  Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II "selective" inhibitor celecoxib.
  in Bioorganic & medicinal chemistry letters (Print)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Di Fiore, Anna; Pedone, Carlo; D'Ambrosio, Katia; Scozzafava, Andrea; De Simone, Giuseppina; Supuran, Claudiu T. (literal)

Pagina inizio

• 437 (literal)

Pagina fine

• 442 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 16 (literal)

Rivista

• Bioorganic & medicinal chemistry letters (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto

• Pubblicazione su rivista internazionale (literal)

Note

• Scopu (literal)
• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Naples, Italy; Dipartimento delle Scienze Biologiche-Sezione Biostrutture, University of Naples \"Federico II\", via Mezzocannone 16, 80134 Naples, Italy; Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy. (literal)

Titolo

• Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II \"selective\" inhibitor celecoxib. (literal)

Abstract

• The high resolution X-ray crystal structure of the adduct of human carbonic anhydrase (CA, EC 4.2.1.1) isoform II (hCA II) with the clinically used painkiller valdecoxib, acting as a potent CA II and cyclooxygenase-2 (COX-2) inhibitor, is reported. The ionized sulfonamide moiety of valdecoxib is coordinated to the catalytic Zn(II) ion with a tetrahedral geometry. The phenyl-isoxazole moiety of the inhibitor fills the active site channel and interacts with the side chains of Gln92, Val121, Leu198, Thr200, and Pro202. Its 3-phenyl group is located into a hydrophobic pocket, simultaneously establishing van der Waals interactions with the aliphatic side chain of various hydrophobic residues (Val135, Ile91, Val121, Leu198, and Leu141) and a strong offset face-to-face stacking interaction with the aromatic ring of Phe131 (the ?1 angle of which is rotated about 90° with respect to what was observed in the structure of the native enzyme and those of other sulfonamide complexes). Celecoxib, a structurally related COX-2 inhibitor for which the X-ray crystal structure was reported earlier, binds in a completely different manner to hCA II as compared to valdecoxib. Celecoxib completely fills the entire CA II active site, with its trifluoromethyl group in the hydrophobic part of the active site and the p-tolyl moiety in the hydrophilic one, not establishing any interaction with Phe131. In contrast to celecoxib, valdecoxib was rotated about 90° around the chemical bond connecting the benzensulfonamide and the substituted isoxazole ring allowing for these multiple favorable interactions. These different binding modes allow for the further drug design of various CA inhibitors belonging to the benzenesulfonamide class. (literal)

Prodotto di

• Institute of biostructure and bioimaging (IBB) (Istituto)
• Determinazione della struttura tridimensionale di biomolecole complesse con tecniche spettroscopiche e cristallografiche (PM.P01.022.001) (Modulo)

Autore CNR

• CARLO PEDONE (Persona)
• GIUSEPPINA DE SIMONE (Unità di personale interno)
• KATIA D'AMBROSIO (Persona)
• ANNA DI FIORE (Persona)

Insieme di parole chiave

• Keywords of "Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II \"selective\" inhibitor celecoxib." (Insieme di parole chiave)

Incoming links:

Autore CNR di

• GIUSEPPINA DE SIMONE (Unità di personale interno)
• CARLO PEDONE (Persona)
• KATIA D'AMBROSIO (Persona)
• ANNA DI FIORE (Persona)

Prodotto

• Institute of biostructure and bioimaging (IBB) (Istituto)
• Determinazione della struttura tridimensionale di biomolecole complesse con tecniche spettroscopiche e cristallografiche (PM.P01.022.001) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Bioorganic & medicinal chemistry letters (Rivista)

Insieme di parole chiave di

• Keywords of "Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II \"selective\" inhibitor celecoxib." (Insieme di parole chiave)