%0 Journal Article
%A Xiong, Jing
%A Xu, Dingguo
%D 2017
%T Insights into the Catalytic Mechanism of Unsaturated
Glucuronyl Hydrolase of Bacillus sp. GL1
%U https://acs.figshare.com/articles/journal_contribution/Insights_into_the_Catalytic_Mechanism_of_Unsaturated_Glucuronyl_Hydrolase_of_i_Bacillus_i_sp_GL1/4585057
%R 10.1021/acs.jpcb.6b10501.s001
%2 https://acs.figshare.com/ndownloader/files/7423624
%K chondroitin disaccharide
%K degradation mechanism
%K enzyme
%K X-ray structures
%K Unsaturated Glucuronyl Hydrolase
%K Catalytic Mechanism
%K metastable oxocarbenium-ion-like
%K chondroitin lyase
%K virulence factors
%K Bacillus sp
%K vinyl ether group
%K PL
%K carbons 4
%K d-glucuronic acid unit
%K glucuronyl hydrolase
%K recognition specificity
%K degradation step
%K GL 1
%K polysaccharide lyases
%K d-galactosamine unit
%K causes extracellular
%K GAG
%K pathway
%K dynamics simulations
%X Together with polysaccharide lyases (PLs), the unsaturated glucuronyl
hydrolase of Bacillus sp., GL1, is responsible for
the metabolism of glycosaminoglycans (GAGs), which plays an important role in various crucial physiological
events. More importantly, the degradation mechanism of GAGs often
causes extracellular bacterial infection and is thought to be one
of the virulence factors. We have previously studied the first degradation
step catalyzed by PLs. In this work, we focused on the degradation
of the unsaturated chondroitin disaccharide, which is produced from
chondroitin by chondroitin lyase.
A combined quantum mechanical and molecular mechanical method was
employed in all simulations. First of all, molecular dynamics simulations
were performed to obtain a stable initial enzyme–substrate
complex structure. Almost all interactions between the substrate and
enzyme were found to be related to the d-glucuronic acid
unit, whereas no recognition specificity was observed for the N-acetyl-d-galactosamine unit.
Experimentally, two different pathways have been proposed on the basis
of X-ray structures and kinetic isotopic effects. In our simulation,
the pathway involving the formation of an epoxide intermediate has
been found to be favorable
rather than that involving direct hydration of the vinyl ether group
around carbons 4 and 5. A metastable oxocarbenium-ion-like intermediate
can be found in our simulation.
%I ACS Publications