Upregulation of an Artificial Zymogen by Proteolysis

Zhe Liu; Vincent Lebrun; Taku Kitanosono; Hendrik Mallin; Valentin Köhler; Daniel Häussinger; Donald Hilvert; Shu Kobayashi; Thomas R Ward

doi:10.1002/anie.201605010

Upregulation of an Artificial Zymogen by Proteolysis

Angew Chem Int Ed Engl. 2016 Sep 12;55(38):11587-90. doi: 10.1002/anie.201605010. Epub 2016 Aug 16.

Authors

Zhe Liu^{1

2}, Vincent Lebrun¹, Taku Kitanosono³, Hendrik Mallin¹, Valentin Köhler¹, Daniel Häussinger¹, Donald Hilvert⁴, Shu Kobayashi³, Thomas R Ward⁵

Affiliations

¹ Department of Chemistry, University of Basel, 4056, Basel, Switzerland.
² School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, P.R. China.
³ Department of Chemistry, School of Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
⁴ Laboratory of Organic Chemistry, ETH Zürich, 8093, Zürich, Switzerland.
⁵ Department of Chemistry, University of Basel, 4056, Basel, Switzerland. thomas.ward@unibas.ch.

PMID: 27529471
DOI: 10.1002/anie.201605010

Abstract

Regulation of enzymatic activity is vital to living organisms. Here, we report the development and the genetic optimization of an artificial zymogen requiring the action of a natural protease to upregulate its latent asymmetric transfer hydrogenase activity.

Keywords: artificial metalloenzyme; artificial zymogen; asymmetric catalysis; transfer hydrogenation; upregulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding Sites
Biomimetic Materials / chemistry
Biomimetic Materials / metabolism
Catalysis
Coordination Complexes / chemistry
Coordination Complexes / metabolism
Enzyme Precursors / chemistry
Enzyme Precursors / genetics*
Enzyme Precursors / metabolism*
Iridium / chemistry
Peptides / chemistry
Peptides / metabolism
Proteolysis
Substrate Specificity
Up-Regulation*

Substances

Coordination Complexes
Enzyme Precursors
Peptides
Iridium