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Identification and computionally-based structural interpretation of naturally occuring variants of human protein C

Authors :
Francesca Marino
Pasqualina D'Ursi
Ermanna Rovida
Sara Zanardelli
Elena M. Faioni
Gessica Fontana
Giancarlo Castaman
Giuliana Merati
Source :
Human mutation 28 (2007): 345–355. doi:10.1002/humu.20445, info:cnr-pdr/source/autori:Ermanna Rovida 1, Giuliana Merati 2, Pasqualina D'Ursi 3, Sara Zanardelli 2, Francesca Marino 1, Gessica Fontana 4, GiancarloCastaman 5, Elena M. Faioni 4/titolo:Identification and computionally-based structural interpretation of naturally occuring variants of human protein C/doi:10.1002%2Fhumu.20445/rivista:Human mutation/anno:2007/pagina_da:345/pagina_a:355/intervallo_pagine:345–355/volume:28, info:cnr-pdr/source/autori:Rovida E; Merati G; D'Ursi P; Zanardelli S; Marino F; Fontana G; Castaman G; Faioni EM/titolo:Identification and computationally-based structural interpretation of naturally occurring variants of human protein C./doi:10.1002%2Fhumu.20445/rivista:Human mutation/anno:2007/pagina_da:345/pagina_a:355/intervallo_pagine:345–355/volume:28
Publication Year :
2007
Publisher :
Wiley-Liss, New York , Stati Uniti d'America, 2007.

Abstract

Protein C (PC) is a key regulator of blood clotting and inflammation. Its inherited deficiency is associated with venous thromboembolism, and recombinant activated PC is currently used to increase survival in severe sepsis. The molecular basis of inherited PC deficiency is heterogeneous. Due to its multiple physiologic interactions and functions, and its modular structure, natural variants aid in the understanding of the relationship between critical residues and discrete functions. This knowledge has important therapeutic implications in the planning of a recombinant activated PC with a specific therapeutic target and devoid of major collateral effects. A way of predicting important functional consequences of residue variation is the use of molecular modeling and structural interpretation of amino acidic substitutions. A study of 21 out of 32 identified PC gene (PROC) variants is presented. For three of them, localized in the active site, electrostatic potential variation was calculated. For more than half of the studied variants, an explanation for the functional impairment could be derived from computational analysis, allowing a focused choice of which variants it is worthwhile pursuing. Hum Mutat 28(4), 345–355, 2007. © 2006 Wiley-Liss, Inc.

Details

Language :
English
Database :
OpenAIRE
Journal :
Human mutation 28 (2007): 345–355. doi:10.1002/humu.20445, info:cnr-pdr/source/autori:Ermanna Rovida 1, Giuliana Merati 2, Pasqualina D'Ursi 3, Sara Zanardelli 2, Francesca Marino 1, Gessica Fontana 4, GiancarloCastaman 5, Elena M. Faioni 4/titolo:Identification and computionally-based structural interpretation of naturally occuring variants of human protein C/doi:10.1002%2Fhumu.20445/rivista:Human mutation/anno:2007/pagina_da:345/pagina_a:355/intervallo_pagine:345–355/volume:28, info:cnr-pdr/source/autori:Rovida E; Merati G; D'Ursi P; Zanardelli S; Marino F; Fontana G; Castaman G; Faioni EM/titolo:Identification and computationally-based structural interpretation of naturally occurring variants of human protein C./doi:10.1002%2Fhumu.20445/rivista:Human mutation/anno:2007/pagina_da:345/pagina_a:355/intervallo_pagine:345–355/volume:28
Accession number :
edsair.doi.dedup.....77b27476a8e8451d128fb7236a52649f
Full Text :
https://doi.org/10.1002/humu.20445