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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2015

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Engineering of Kuma030: a gliadin peptidase that rapidly degrades immunogenic gliadin peptides in gastric conditions

Anno di pubblicazione: 2015

Formato: Elettronico

Autori: Clancey Wolf, Justin B Siegel, Christine Tinberg, Alessandra Camarca, Carmen Gianfrani, Shirley Paski, David Baker, Ingrid S Pultz1

Affiliazioni autori: Department of Biochemistry, University of Washington, Seattle, Washington, USA; Departments of Chemistry, Biochemistry, and Molecular Medicine, University of California-Davis, Davis, California, USA; Institute of Food Science-CNR, Avellino, Italy; Department of Gastroenterology, University of Washington Medical Center, Seattle, Washington, USA

Autori CNR:

  • ALESSANDRA CAMARCA
  • CARMELA GIANFRANI

Lingua: inglese

Abstract: Celiac disease is characterized by intestinal inflammation triggered by gliadin, a component of dietary gluten. Oral administration of proteases that can rapidly degrade gliadin in the gastric compartment has been proposed as a treatment for celiac disease; however, no protease has been shown to specifically reduce the immunogenic gliadin content, in gastric conditions, to below the threshold shown to be toxic for celiac patients. Here, we used the Rosetta Molecular Modeling Suite to redesign the active site of the acid-active gliadin endopeptidase KumaMax. The resulting protease, Kuma030, specifically recognizes tripeptide sequences that are found throughout the immunogenic regions of gliadin, as well as in homologous proteins in barley and rye. Indeed, treatment of gliadin with Kuma030 eliminates the ability of gliadin to stimulate a T cell response. Kuma030 is capable of degrading >99% of the immunogenic gliadin fraction in laboratory-simulated gastric digestions with minutes, to a level below the toxic threshold for celiac patients, suggesting great potential for this enzyme as an oral therapeutic for celiac disease.

Lingua abstract: inglese

Rivista:

Journal of the American Chemical Society American Chemical Society,
Paese di pubblicazione: Stati Uniti d'America
Lingua: inglese
ISSN: 1520-5126

Referee: Sė: Internazionale

Stato della pubblicazione: Published version

Indicizzato da: PubMed [PMID: 26374198]

Parole chiave:

  • gliadin
  • peptidase
  • celiac disease

Strutture CNR:

Moduli:

 
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