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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2012

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Correlation assessment among clinical phenotypes, expression analysis and molecular modeling of 14 novel variations in the human galactose-1-phosphate uridylyltransferase gene.

Anno di pubblicazione: 2012

Formato: Elettronico Cartaceo

Autori: Tang M, Facchiano A, Rachamadugu R, Calderon F, Mao R, Milanesi L, Marabotti A, Lai K

Affiliazioni autori: TM, RR, LK: Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, Utah; FA: Laboratory of Bioinformatics and Computational Biology, Institute of Food Science--CNR, Avellino, Italy; CF MR: ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah; ML, MA: Laboratory of Bioinformatics, Institute of Biomedical Technologies--CNR, Segrate, Italy

Autori CNR:


Lingua: inglese

Abstract: Galactose-1-phosphate uridylyltransferase (GALT) catalyzes the conversion of galactose-1-phosphate to UDP-galactose, a key step in the galactose metabolism. Deficiency of GALT activity in humans caused by deleterious variations in the GALT gene can cause a potentially lethal disease called classic galactosemia. In this study, we selected 14 novel nucleotide sequence changes in the GALT genes found in galactosemic patients for expression analysis and molecular modeling. Several variants showed decreased levels of expression and decreased abundance in the soluble fraction of the Escherichia coli cell extracts, suggesting altered stability and solubility. Only six variant GALT enzymes had detectable enzymatic activities. Kinetic studies showed that their V max decreased significantly. To further characterize the variants at molecular level, we performed static and dynamic molecular modeling studies. Effects of variations on local and/or global structural features of the enzyme were anticipated for the majority of variants. In-depth studies with molecular dynamic simulations on selected variants predicted the alteration of the protein structure even though static models apparently did not highlight any perturbation. Overall, these studies offered new insights on the molecular properties of GALT enzyme, with the aim of correlating them with the clinical outcome.

Lingua abstract: inglese

Pagine da: 1107

Pagine a: 1115


Human mutation Wiley-Liss,
Paese di pubblicazione: Stati Uniti d'America
Lingua: inglese
ISSN: 1059-7794

Numero volume: 33

Numero fascicolo: 7

DOI: 10.1002/humu.22093

Referee: Sė: Internazionale

Indicizzato da:

  • PubMed [22461411]
  • ISI Web of Science (WOS) [000304815100015]
  • Scopus [2-s2.0-84861886186]

Strutture CNR:


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