English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Unravelling the Molecular Origin of the Regiospecificity in Extradiol Catechol Dioxygenases

MPS-Authors

Christian,  Gemma J.
Research Department Neese, Max Planck Institute for Chemical Energy Conversion, Max Planck Society;
Avondale College of Higher Education, Cooranbon;

/persons/resource/persons216825

Neese,  Frank
Research Department Neese, Max Planck Institute for Chemical Energy Conversion, Max Planck Society;

/persons/resource/persons216845

Ye,  Shengfa
Research Department Neese, Max Planck Institute for Chemical Energy Conversion, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Christian, G. J., Neese, F., & Ye, S. (2016). Unravelling the Molecular Origin of the Regiospecificity in Extradiol Catechol Dioxygenases. Inorganic Chemistry, 55(8), 3853-3864. doi:10.1021/acs.inorgchem.5b02978.


Cite as: http://hdl.handle.net/21.11116/0000-0007-84F7-D
Abstract
Many factors have been suggested to control the selectivity for extradiol or intradiol cleavage in catechol dioxygenases. The varied selectivity of model complexes and the ability to force an extradiol enzyme to do intradiol cleavage indicate that the problem may be complex. In this paper we focus on the regiospecificity of the proximal extradiol dioxygenase, homoprotocatechuate 2,3-dioxygenase (HPCD), for which considerable advances have been made in our understanding of the mechanism from an experimental and computational standpoint. Two key steps in the reaction mechanism were investigated: (1) attack of the substrate by the superoxide moiety and (2) attack of the substrate by the oxyl radical generated by O–O bond cleavage. The selectivity at both steps was investigated through a systematic study of the role of the substrate and the first and second coordination spheres. For the isolated native substrate, intradiol cleavage is calculated to be both kinetically and thermodynamically favored, therefore nature must use the enzyme environment to reverse this preference. Two second sphere residues were found to play key roles in controlling the regiospecificity of the reaction: Tyr257 and His200. Tyr257 controls the selectivity by modulating the electronic structure of the substrate, while His200 controls selectivity through steric effects and by preventing alternative pathways to intradiol cleavage.