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Lookup NU author(s): Dr Fiona Cuskin,
Emeritus Professor Harry Gilbert
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
The enzymatic cleavage of beta-1,4-mannans is achieved by endo-beta-1,4-mannanases, enzymes involved in germination of seeds and microbial hemicellulose degradation, and which have increasing industrial and consumer product applications. beta-Mannanases occur in a range of families of the CAZy sequence-based glycoside hydrolase (GH) classification scheme including families 5, 26, and 113. In this work we reveal that beta-mannanases of the newly described GH family 134 differ from other mannanase families in both their mechanism and tertiary structure. A representative GH family 134 endo-beta-1,4-mannanase from a Streptomyces sp. displays a fold closely related to that of hen egg white lysozyme but acts with inversion of stereochemistry. A Michaelis complex with mannopentaose, and a product complex with mannotriose, reveal ligands with pyranose rings distorted in an unusual inverted chair conformation. Ab initio quantum mechanics/molecular mechanics metadynamics quantified the energetically accessible ring conformations and provided evidence in support of a C-1(4) -> H-3(4)double dagger -> S-3(1) conformational itinerary along the reaction coordinate. This work, in concert with that on GH family 124 cellulases, reveals how the lysozyme fold can be co-opted to catalyze the hydrolysis of different polysaccharides in a mechanistically distinct manner.
Author(s): Jin Y, Petricevic M, John A, Raich L, Jenkins H, De Souza LP, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, Davies GJ
Publication type: Article
Publication status: Published
Journal: ACS Central Science
Online publication date: 08/01/2016
Acceptance date: 01/01/1900
Date deposited: 02/03/2017
ISSN (print): 2374-7943
ISSN (electronic): 2374-7951
Publisher: American Chemical Society
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