http://www.cnr.it/ontology/cnr/individuo/prodotto/ID213053
Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation (Articolo in rivista)
- Type
- Label
- Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation (Articolo in rivista) (literal)
- Anno
- 2013-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- Alternative label
Giuseppina Andreotti1, Emilia Pedone2, Assunta Giordano1 & Maria Vittoria Cubellis2,3 (2013)
Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation
in MOLECULAR GENETICS & GENOMIC MEDICINE
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Giuseppina Andreotti1, Emilia Pedone2, Assunta Giordano1 & Maria Vittoria Cubellis2,3 (literal)
- Pagina inizio
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- 1Istituto di Chimica Biomolecolare - CNR, Pozzuoli, Italy
2Istituto di Biostrutture e Bioimmagini - CNR, Napoli, Italy
3Dipartimento di Biologia, Universita' Federico II, Napoli, Italy (literal)
- Titolo
- Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation (literal)
- Abstract
- Phosphomannomutase 2 (PMM2) deficiency represents the most frequent type
of congenital disorders of glycosylation. For this disease there is no cure at
present. The complete loss of phosphomannomutase activity is probably not
compatible with life and people affected carry at least one allele with residual
activity. We characterized wild-type PMM2 and its most common hypomorphic
mutant, p.F119L, which is associated with a severe phenotype of the disease.
We demonstrated that active species is the dimeric enzyme and that the mutation
weakens the quaternary structure and, at the same time, affects the activity
and the stability of the enzyme. We demonstrated that ligand binding stabilizes
both proteins, wild-type and F119L-PMM2, and promotes subunit association
in vitro. The strongest effects are observed with glucose-1,6-bisphosphate
(Glc-1,6-P2) or with monophosphate glucose in the presence of vanadate. This
finding offers a new approach for the treatment of PMM2 deficiency. We
propose to enhance Glc-1,6-P2 concentration either acting on the metabolic
pathways that control its synthesis and degradation or exploiting prodrugs that
are able to cross membranes. (literal)
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