Publication
Article Metrics
Citations
Online attention
A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism
DOI:
10.1021/acscentsci.6b00232
Authors:
Yi
Jin
(University of York)
,
Marija
Petricevic
(University of Melbourne)
,
Alan
John
(University of Melbourne)
,
Lluís
Raich
(Departament de Química Inorgànica i Orgànica (Secció de Química Orgànica) & IQTCUB, Universitat de Barcelona)
,
Huw
Jenkins
(University of York)
,
Leticia
Portela De Souza
(University of York)
,
Fiona
Cuskin
(Newcastle University)
,
Harry J.
Gilbert
(Newcastle University)
,
Carme
Rovira
(Universitat de Barcelona; Institució Catalana de Recerca i Estudis Avançats (ICREA))
,
Ethan D.
Goddard-borger
(ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research; University of Melbourne)
,
Spencer J.
Williams
(University of Melbourne)
,
Gideon J.
Davies
(University of York)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Acs Central Science
State:
Published (Approved)
Published:
November 2016
Diamond Proposal Number(s):
9948
Abstract: The enzymatic cleavage of β-1,4-mannans is achieved by endo-β-1,4-mannanases, enzymes involved in germination of seeds and microbial hemicellulose degradation, and which have increasing industrial and consumer product applications. β-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 β-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-β-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 1C4 → 3H4‡ → 3S1 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.
Subject Areas:
Biology and Bio-materials,
Chemistry
Instruments:
I02-Macromolecular Crystallography