Publication Abstract from PubMed
The modification of N-glycans by alpha-mannosidases is a process that is relevant to a large number of biologically important processes, including infection by microbial pathogens and colonization by microbial symbionts. At present, described mannosidases that are specific for alpha-1,6-mannose linkages are very limited in number. Through structural and functional analysis of two sequence related enzymes, one from Streptococcus pneumoniae (SpGHX) and one from Clostridium perfringens (CpGHX), a new glycoside hydrolase family, GHX, is identified and characterized. Analysis of SpGHX and CpGHX reveal them to have exo-alpha-1,6-mannosidase activity consistent with specificity for N-linked glycans having their alpha-1,3-mannose branches removed. The X-ray crystal structures of SpGHX and CpGHX obtained in apo-, inhibitor bound, and substrate bound forms provide both mechanistic and molecular insight into how these proteins, which adopt an (alpha/alpha)6-fold, recognize and hydrolyze the alpha-1,6-mannosidic bond by an inverting, metal-independent catalytic mechanism. A phylogenetic analysis of GHX proteins reveals this to be a relatively large and widespread family found frequently in bacterial pathogens, bacterial human gut symbionts, and a variety of fungi. Based on these studies we predict this family of enzymes will primarily comprise such exo-alpha-1,6-mannosidases.
Analysis of new family of widely distributed metal-independent {alpha}-mannosidases provides unique insight into the processing of N-linked glycans.,Gregg KJ, Zandberg WF, Hehemann JH, Whitworth GE, Deng L, Vocadlo DJ, Boraston AB J Biol Chem. 2011 Mar 9. PMID:21388958[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
