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Titolo:
Structural evidence for a functional role of human tissue nonspecific alkaline phosphatase in bone mineralization
Autore:
Mornet, E; Stura, E; Lia-Baldini, AS; Stigbrand, T; Menez, A; Le Du, MH;
Indirizzi:
CE Saclay, CEA, DIEP, F-91191 Gif Sur Yvette, France CE Saclay Gif Sur Yvette France F-91191 , F-91191 Gif Sur Yvette, France Umea Univ, Dept Immunol, Umea, Sweden Umea Univ Umea SwedenUmea Univ, Dept Immunol, Umea, Sweden Univ Versailles, Ctr Etud Biol Prenatale, SESEP, F-78000 Versailles, France Univ Versailles Versailles France F-78000 EP, F-78000 Versailles, France
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 33, volume: 276, anno: 2001,
pagine: 31171 - 31178
SICI:
0021-9258(20010817)276:33<31171:SEFAFR>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
INFANTILE HYPOPHOSPHATASIA; LETHAL HYPOPHOSPHATASIA; MISSENSE MUTATION; GENE; CALCIUM; LOCALIZATION; MECHANISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Le Du, MH CE Saclay, CEA, DIEP, F-91191 Gif Sur Yvette, France CE Saclay Gif Sur Yvette France F-91191 Gif Sur Yvette, France
Citazione:
E. Mornet et al., "Structural evidence for a functional role of human tissue nonspecific alkaline phosphatase in bone mineralization", J BIOL CHEM, 276(33), 2001, pp. 31171-31178

Abstract

The human tissue nonspecific alkaline phosphatase (TNAP) is found in liver, kidney, and bone. Mutations in the TNAP gene can lead to Hypophosphatasia, a rare inborn disease that is characterized by defective bone mineralization. TNAP is 74% homologous to human placental alkaline phosphatase (PLAP) whose crystal structure has been recently determined at atomic resolution (Le Du, M. H., Stigbrand, T., Taussig, M. J., Menez, A., and Stura, E. A. (2001) J. Biol. Chem, 276,9158-9165). The degree of homology allowed us to build a reliable TNAP model to investigate the relationship between mutationsassociated with hypophosphatasia and their probable consequences on the activity or the structure of the enzyme. The mutations are clustered within five crucial regions, namely the active site and its vicinity, the active site valley, the homodimer interface, the crown domain, and the metal-bindingsite. The crown domain and the metal-binding domain are mammalian-specificand were observed for the first time in the PLAP structure. The crown domain contains a collagen binding loop. A synchrotron radiation x-ray fluorescence study confirms that the metal in the metal-binding site is a calcium ion. Several severe mutations in TNAP occur around this calcium site, suggesting that calcium may be of critical importance for the TNAP function. The presence of this extra metal-binding site gives new insights on the controversial role observed for calcium.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 04:26:45