Advanced

Multiscale Modelling of Lytic Polysaccharide Monooxygenases

Hedegård, Erik LU and Ryde, Ulf LU (2017) In ACS Omega 2. p.536-545
Abstract
Lytic polysaccharide monooxygenase (LPMO) enzymes have attracted considerable attention owing to their ability to enhance polysaccharide depolymerization, making them interesting with respect to production of biofuel from cellulose. LPMOs are metalloenzymes that contain a mononuclear copper active site, capable of activating dioxygen. However, many details of this activation are unclear. Some aspects of the mechanism have previously been investigated from a computational angle. Yet, either these studies have employed only molecular mechanics (MM), which are inaccurate for metal active sites, or they have described only the active site with quantum mechanics (QM) and neglected the effect of the protein. Here, we employ hybrid QM and MM... (More)
Lytic polysaccharide monooxygenase (LPMO) enzymes have attracted considerable attention owing to their ability to enhance polysaccharide depolymerization, making them interesting with respect to production of biofuel from cellulose. LPMOs are metalloenzymes that contain a mononuclear copper active site, capable of activating dioxygen. However, many details of this activation are unclear. Some aspects of the mechanism have previously been investigated from a computational angle. Yet, either these studies have employed only molecular mechanics (MM), which are inaccurate for metal active sites, or they have described only the active site with quantum mechanics (QM) and neglected the effect of the protein. Here, we employ hybrid QM and MM (QM/MM) methods to investigate the first steps of the LPMO mechanism, which is reduction of CuII to CuI and the formation of a CuII–superoxide complex. In the latter complex, the superoxide can bind either in an equatorial or an axial position. For both steps, we obtain structures that are markedly different from previous suggestions, based on small QM-cluster calculations. Our calculations show that the equatorial isomer of the superoxide complex is over 60 kJ/mol more stable than the axial isomer because it is stabilized by interactions with a second-coordination-sphere glutamine residue, suggesting a possible role for this residue. The coordination of superoxide in this manner agrees with recent experimental suggestions. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Coordination chemistry, Molecular dynamics simulation, Molecular mechanics, Molecular structure, Proteins, Reaction mechanism, Theory
in
ACS Omega
volume
2
pages
536 - 545
publisher
American Chemical Society (ACS)
external identifiers
  • scopus:85028937910
  • wos:000395863300020
ISSN
2470-1343
DOI
10.1021/acsomega.6b00521
language
English
LU publication?
yes
id
5bce233c-7381-4f23-a6b0-5c790fc0075e
date added to LUP
2017-07-27 14:50:56
date last changed
2018-05-20 04:36:15
@article{5bce233c-7381-4f23-a6b0-5c790fc0075e,
  abstract     = {Lytic polysaccharide monooxygenase (LPMO) enzymes have attracted considerable attention owing to their ability to enhance polysaccharide depolymerization, making them interesting with respect to production of biofuel from cellulose. LPMOs are metalloenzymes that contain a mononuclear copper active site, capable of activating dioxygen. However, many details of this activation are unclear. Some aspects of the mechanism have previously been investigated from a computational angle. Yet, either these studies have employed only molecular mechanics (MM), which are inaccurate for metal active sites, or they have described only the active site with quantum mechanics (QM) and neglected the effect of the protein. Here, we employ hybrid QM and MM (QM/MM) methods to investigate the first steps of the LPMO mechanism, which is reduction of CuII to CuI and the formation of a CuII–superoxide complex. In the latter complex, the superoxide can bind either in an equatorial or an axial position. For both steps, we obtain structures that are markedly different from previous suggestions, based on small QM-cluster calculations. Our calculations show that the equatorial isomer of the superoxide complex is over 60 kJ/mol more stable than the axial isomer because it is stabilized by interactions with a second-coordination-sphere glutamine residue, suggesting a possible role for this residue. The coordination of superoxide in this manner agrees with recent experimental suggestions.},
  author       = {Hedegård, Erik and Ryde, Ulf},
  issn         = {2470-1343},
  keyword      = { Coordination chemistry,Molecular dynamics simulation,Molecular mechanics,Molecular structure, Proteins, Reaction mechanism,Theory},
  language     = {eng},
  pages        = {536--545},
  publisher    = {American Chemical Society (ACS)},
  series       = {ACS Omega},
  title        = {Multiscale Modelling of Lytic Polysaccharide Monooxygenases},
  url          = {http://dx.doi.org/10.1021/acsomega.6b00521},
  volume       = {2},
  year         = {2017},
}