Inter-domain electron transfer in cellobiose dehydrogenase: modulation by pH and divalent cations
(2015) In The FEBS Journal 282(16). p.3136-3148- Abstract
- The flavocytochrome cellobiose dehydrogenase (CDH) is secreted by wood-decomposing fungi, and is the only known extracellular enzyme with the characteristics of an electron transfer protein. Its proposed function is reduction of lytic polysaccharide mono-oxygenase for subsequent cellulose depolymerization. Electrons are transferred from FADH(2) in the catalytic flavodehydrogenase domain of CDH to haemb in a mobile cytochrome domain, which acts as a mediator and transfers electrons towards the active site of lytic polysaccharide mono-oxygenase to activate oxygen. This vital role of the cytochrome domain is little understood, e.g. why do CDHs exhibit different pH optima and rates for inter-domain electron transfer (IET)? This study uses... (More)
- The flavocytochrome cellobiose dehydrogenase (CDH) is secreted by wood-decomposing fungi, and is the only known extracellular enzyme with the characteristics of an electron transfer protein. Its proposed function is reduction of lytic polysaccharide mono-oxygenase for subsequent cellulose depolymerization. Electrons are transferred from FADH(2) in the catalytic flavodehydrogenase domain of CDH to haemb in a mobile cytochrome domain, which acts as a mediator and transfers electrons towards the active site of lytic polysaccharide mono-oxygenase to activate oxygen. This vital role of the cytochrome domain is little understood, e.g. why do CDHs exhibit different pH optima and rates for inter-domain electron transfer (IET)? This study uses kinetic techniques and docking to assess the interaction of both domains and the resulting IET with regard to pH and ions. The results show that the reported elimination of IET at neutral or alkaline pH is caused by electrostatic repulsion, which prevents adoption of the closed conformation of CDH. Divalent alkali earth metal cations are shown to exert a bridging effect between the domains at concentrations of >3mm, thereby neutralizing electrostatic repulsion and increasing IET rates. The necessary high ion concentration, together with the docking results, show that this effect is not caused by specific cation binding sites, but by various clusters of Asp, Glu, Asn, Gln and the haemb propionate group at the domain interface. The results show that a closed conformation of both CDH domains is necessary for IET, but the closed conformation also increases the FAD reduction rate by an electron pulling effect. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7972293
- author
- Kracher, Daniel ; Zahma, Kawah ; Schulz, Christopher LU ; Sygmund, Christoph ; Gorton, Lo LU and Ludwig, Roland
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- oxidative cellulose degradation, inter-domain electron transfer, docking, domain, divalent cation bridging effect, cellobiose dehydrogenase
- in
- The FEBS Journal
- volume
- 282
- issue
- 16
- pages
- 3136 - 3148
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000360016700011
- scopus:84939252292
- pmid:25913436
- ISSN
- 1742-464X
- DOI
- 10.1111/febs.13310
- language
- English
- LU publication?
- yes
- id
- b3d3fa4c-4bb0-4d3e-a2c3-4e7d1383bf77 (old id 7972293)
- date added to LUP
- 2016-04-01 13:46:30
- date last changed
- 2022-04-14 03:05:19
@article{b3d3fa4c-4bb0-4d3e-a2c3-4e7d1383bf77,
abstract = {{The flavocytochrome cellobiose dehydrogenase (CDH) is secreted by wood-decomposing fungi, and is the only known extracellular enzyme with the characteristics of an electron transfer protein. Its proposed function is reduction of lytic polysaccharide mono-oxygenase for subsequent cellulose depolymerization. Electrons are transferred from FADH(2) in the catalytic flavodehydrogenase domain of CDH to haemb in a mobile cytochrome domain, which acts as a mediator and transfers electrons towards the active site of lytic polysaccharide mono-oxygenase to activate oxygen. This vital role of the cytochrome domain is little understood, e.g. why do CDHs exhibit different pH optima and rates for inter-domain electron transfer (IET)? This study uses kinetic techniques and docking to assess the interaction of both domains and the resulting IET with regard to pH and ions. The results show that the reported elimination of IET at neutral or alkaline pH is caused by electrostatic repulsion, which prevents adoption of the closed conformation of CDH. Divalent alkali earth metal cations are shown to exert a bridging effect between the domains at concentrations of >3mm, thereby neutralizing electrostatic repulsion and increasing IET rates. The necessary high ion concentration, together with the docking results, show that this effect is not caused by specific cation binding sites, but by various clusters of Asp, Glu, Asn, Gln and the haemb propionate group at the domain interface. The results show that a closed conformation of both CDH domains is necessary for IET, but the closed conformation also increases the FAD reduction rate by an electron pulling effect.}},
author = {{Kracher, Daniel and Zahma, Kawah and Schulz, Christopher and Sygmund, Christoph and Gorton, Lo and Ludwig, Roland}},
issn = {{1742-464X}},
keywords = {{oxidative cellulose degradation; inter-domain electron transfer; docking; domain; divalent cation bridging effect; cellobiose dehydrogenase}},
language = {{eng}},
number = {{16}},
pages = {{3136--3148}},
publisher = {{Wiley-Blackwell}},
series = {{The FEBS Journal}},
title = {{Inter-domain electron transfer in cellobiose dehydrogenase: modulation by pH and divalent cations}},
url = {{http://dx.doi.org/10.1111/febs.13310}},
doi = {{10.1111/febs.13310}},
volume = {{282}},
year = {{2015}},
}