Artículo
Structure, mechanism, and dynamics of UDP-galactopyranose mutase
Fecha de publicación:
10/2014
Editorial:
Elsevier Inc
Revista:
Archives of Biochemistry and Biophysics
ISSN:
0003-9861
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The flavoenzyme UDP-galactopyranose mutase (UGM) is a key enzyme in galactofuranose biosynthesis. The enzyme catalyzes the 6-to-5 ring contraction of UDP-galactopyranose to UDP-galactofuranose. Galactofuranose is absent in humans yet is an essential component of bacterial and fungal cell walls and a cell surface virulence factor in protozoan parasites. Thus, inhibition of galactofuranose biosynthesis is a valid strategy for developing new antimicrobials. UGM is an excellent target in this effort because the product of the UGM reaction represents the first appearance of galactofuranose in the biosynthetic pathway. The UGM reaction is redox neutral, which is atypical for flavoenzymes, motivating intense examination of the chemical mechanism and structural features that tune the flavin for its unique role in catalysis. These studies show that the flavin functions as nucleophile, forming a flavin–sugar adduct that facilitates galactose-ring opening and contraction. The 3-dimensional fold is novel and conserved among all UGMs, however the larger eukaryotic enzymes have additional secondary structure elements that lead to significant differences in quaternary structure, substrate conformation, and conformational flexibility. Here we present a comprehensive review of UGM three-dimensional structure, provide an update on recent developments in understanding the mechanism of the enzyme, and summarize computational studies of active site flexibility.
Palabras clave:
Chagas
,
Ugm
,
Molecular Dynamics
,
Conformational Changes
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(OCA CIUDAD UNIVERSITARIA)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA
Citación
Sobrado, Pablo; McCammon, J. Andrew; Boechi, Leonardo; Tanner, John J.; Structure, mechanism, and dynamics of UDP-galactopyranose mutase; Elsevier Inc; Archives of Biochemistry and Biophysics; 544; 10-2014; 128-141
Compartir
Altmétricas