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Identification and computionally-based structural interpretation of naturally occuring variants of human protein C
- 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.
- Subjects :
- Adult
Male
Models, Molecular
Adolescent
Molecular model
Protein Conformation
Molecular Sequence Data
venous thromboembolism
Regulator
Computational biology
Biology
Bioinformatics
law.invention
law
Genetics
medicine
Animals
Humans
Amino Acid Sequence
Child
Gene
Genetics (clinical)
Aged
molecular modeling
Genetic Variation
Active site
PROC
Middle Aged
Protein Structure, Tertiary
Recombinant DNA
biology.protein
electrostatic potential calculation
Protein C variants identification
Female
Identification (biology)
Sequence Alignment
Venous thromboembolism
Protein C
medicine.drug
Subjects
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