Glycosylation is crucial for a proper catalytic site organization in human glucocerebrosidase.
Glycoconj J
; 33(2): 237-44, 2016 Apr.
Article
en En
| MEDLINE
| ID: mdl-27023912
ABSTRACT
Gaucher disease, an autosomal recessive disorder, is caused by a deficiency of glucocerebrosidase (GCase) enzyme, a peripheral membrane-associated glycoprotein that hydrolyses glucosylceramide in lysosomes. Glycosylation is essential for the development of a catalytically active enzyme, specifically in the first site, located at Asn19. However, both the molecular basis of the relevance of N-glycosylation over GCase activity and the effects of glycosylation over its structure and dynamics are still not fully understood. Thus, the present work evaluated GCase enzyme in increasing glycosylation content using triplicate unbiased molecular dynamics simulations. Accordingly, the N-linked glycan chains caused local conformational stabilization effects over the protein, as well as in regions flanking the enzyme catalytic dyad. In the case of the Asn19-linked glycan, it also occurred around region 438-444, where one of the most prevalent GCase mutations is found. Markedly, an increasing catalytic dyad organization was related to increasing glycosylation contents, offering the first atomic-level explanation for the experimental observation that GCase activity is controlled by glycosylation, especially at Asn19.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Simulación de Dinámica Molecular
/
Glucosilceramidasa
Límite:
Humans
Idioma:
En
Revista:
Glycoconj J
Asunto de la revista:
BIOQUIMICA
/
METABOLISMO
Año:
2016
Tipo del documento:
Article
País de afiliación:
Brasil