A fundamental catalytic difference between zinc and manganese dependent enzymes revealed in a bacterial isatin hydrolase

DOI: 10.1038/s41598-018-31259-y

Authors: Theis Sommer (University of Oslo) , Kaare Bjerregaard-Andersen (University of Oslo) , Lalita Uribe (Johannes Gutenberg-Universität Mainz) , Michael Etzerodt (Aarhus University) , Gregor Diezemann (Johannes Gutenberg-Universität Mainz) , Jürgen Gauss (Johannes Gutenberg-Universität Mainz) , Michele Cascella (University of Oslo) , J. Preben Morth (University of Oslo; Oslo University Hospital; Technical University of Denmark)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Scientific Reports , VOL 8

State: Published (Approved)
Published: August 2018
Diamond Proposal Number(s): 9107

Abstract: The catalytic mechanism of the cyclic amidohydrolase isatin hydrolase depends on a catalytically active manganese in the substrate-binding pocket. The Mn2+ ion is bound by a motif also present in other metal dependent hydrolases like the bacterial kynurenine formamidase. The crystal structures of the isatin hydrolases from Labrenzia aggregata and Ralstonia solanacearum combined with activity assays allow for the identification of key determinants specific for the reaction mechanism. Active site residues central to the hydrolytic mechanism include a novel catalytic triad Asp-His-His supported by structural comparison and hybrid quantum mechanics/classical mechanics simulations. A hydrolytic mechanism for a Mn2+ dependent amidohydrolases that disfavour Zn2+ as the primary catalytically active site metal proposed here is supported by these likely cases of convergent evolution. The work illustrates a fundamental difference in the substrate-binding mode between Mn2+ dependent isatin hydrolase like enzymes in comparison with the vast number of Zn2+ dependent enzymes.

Journal Keywords: Catalytic mechanisms; Computational models; X-ray crystallography

Diamond Keywords: Enzymes; Bacteria

Subject Areas: Chemistry, Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography

Other Facilities: ESRF; PETRA III

Added On: 06/09/2018 09:46

Documents:
s41598-018-31259-y.pdf

Discipline Tags:

Biochemistry Catalysis Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)