3QT9

Analysis of a new family of widely distributed metal-independent alpha mannosidases provides unique insight into the processing of N-linked glycans, Clostridium perfringens CPE0426 complexed with alpha-1,6-linked 1-thio-alpha-mannobiose

Summary for 3QT9

• Entry DOI: 10.2210/pdb3qt9/pdb
• Related: 3QT3
• Related PRD ID: PRD_900106
• Descriptor: Putative uncharacterized protein CPE0426, alpha-D-mannopyranose-(1-6)-6-thio-alpha-D-mannopyranose, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: alpha-alpha six fold, glycoside hydrolase, mannosidase, hydrolase
• Biological source: Clostridium perfringens
• Total number of polymer chains: 1
• Total formula weight: 50569.71

Authors

Gregg, K.J.,Zandberg, W.F.,Hehemann, J.-H.,Whitworth, G.E.,Deng, L.E.,Vocadlo, D.J.,Boraston, A.B. (deposition date: 2011-02-22, release date: 2011-03-09, Last modification date: 2024-02-21)

Primary citation

Gregg, K.J.,Zandberg, W.F.,Hehemann, J.H.,Whitworth, G.E.,Deng, L.,Vocadlo, D.J.,Boraston, A.B.
Analysis of a New Family of Widely Distributed Metal-independent {alpha}-Mannosidases Provides Unique Insight into the Processing of N-Linked Glycans.
J.Biol.Chem., 286:15586-15596, 2011

PubMed Abstract: The modification of N-glycans by α-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, the described mannosidases specific for α1,6-mannose linkages are very limited in number. Through structural and functional analysis of two sequence-related enzymes, one from Streptococcus pneumoniae (SpGH125) and one from Clostridium perfringens (CpGH125), a new glycoside hydrolase family, GH125, is identified and characterized. Analysis of SpGH125 and CpGH125 reveal them to have exo-α1,6-mannosidase activity consistent with specificity for N-linked glycans having their α1,3-mannose branches removed. The x-ray crystal structures of SpGH125 and CpGH125 obtained in apo-, inhibitor-bound, and substrate-bound forms provide both mechanistic and molecular insight into how these proteins, which adopt an (α/α)(6)-fold, recognize and hydrolyze the α1,6-mannosidic bond by an inverting, metal-independent catalytic mechanism. A phylogenetic analysis of GH125 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-α1,6-mannosidases.

PubMed: 21388958
DOI: 10.1074/jbc.M111.223172

Experimental method

X-RAY DIFFRACTION (2.05 Å)