A beta-mannanase with a lysozyme-like fold and a novel molecular catalytic mechanism

Jin, Y; Petricevic, M; John, A; Raich, L; Jenkins, H; Portela De Souza, L; Cuskin, F; Gilbert, HJ; Rovira, C; Goddard-Borger, ED; Williams, SJ; Davies, GJ

Author(s): Jin, Y; Petricevic, M; John, A; Raich, L; Jenkins, H; Portela De Souza, L; Cuskin, F; Gilbert, HJ; Rovira, C; Goddard-Borger, ED; Williams, SJ; Davies, GJ;
Details: Publication Year 2016-12-28,Volume 2,Issue #12,Page 896-903
Journal Title: ACS Cent Sci
Publication Type: Journal Article
Abstract: 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 1C4 --> 3H4double dagger --> 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.
Publisher: ACS
Research Division(s): Chemical Biology
PubMed ID: 28058278
Link To PubMed Central Version: https://www-ncbi-nlm-nih-gov/pmc/articles/PMC5200933/
Publisher's Version: https://doi.org/10.1021/acscentsci.6b00232
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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Last Modified: 2017-05-26 03:56:56