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

Scientific Reports
Theis SommerJens Preben Morth

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.

References

Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·O HerzbergD Dunaway-Mariano
Mar 1, 1985·Physical Review A: General Physics·W G Hoover
Sep 15, 1988·Physical Review A: General Physics·A D Becke
Jul 15, 1996·Physical Review. B, Condensed Matter·S GoedeckerJ Hutter
Nov 25, 1985·Physical Review Letters·R Car, M Parrinello
Sep 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alessandro Laio, Michele Parrinello
Dec 18, 2002·Journal of Bacteriology·Scott B Mulrooney, Robert P Hausinger
Nov 1, 2003·FEMS Microbiology Letters·Oleg KurnasovAndrei Osterman
Sep 30, 2004·Journal of the American Chemical Society·Matteo Dal PeraroPaolo Carloni
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Mar 18, 2005·Journal of the American Chemical Society·Michele CascellaPaolo Carloni
Apr 27, 2005·Biochemistry·Clara M Seibert, Frank M Raushel
Oct 21, 2005·Stress : the International Journal on the Biology of Stress·Alexei MedvedevVivette Glover
Jan 11, 2007·Journal of the American Chemical Society·Marco De VivoMichael L Klein
Feb 20, 2007·Journal of the American Chemical Society·Matteo Dal PeraroMichael L Klein
Sep 25, 2007·The Journal of Chemical Physics·Joost VandeVondele, Jürg Hutter
Feb 1, 2008·Physical Review Letters·Alessandro BarducciMichele Parrinello
Apr 22, 2008·Nucleic Acids Research·A DereeperO Gascuel
May 2, 2008·Journal of Molecular Biology·Birgit AndersenJure Piskur
Oct 4, 2008·Journal of the American Chemical Society·Zhenxin HuMichael W Crowder
Nov 5, 2008·Journal of the American Chemical Society·Leticia I LlarrullAlejandro J Vila
Jan 20, 2009·Bioinformatics·Andrew M WaterhouseGeoffrey J Barton
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Nov 26, 2009·Nature Chemical Biology·Andrea K WernerClaus-Peter Witte
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·T Geoff G BattyeAndrew G W Leslie
Jul 9, 2011·The Protein Journal·Ya-Yeh HoCheng-Yang Huang
Apr 26, 2012·Journal of Computer-aided Molecular Design·Jacopo SgrignaniRoberta Pierattelli
Aug 21, 2012·Journal of Bacteriology·Sergio Martínez-RodríguezJose Antonio Gavira
Aug 28, 2013·Journal of Molecular Evolution·Matthieu BarbaBernard Labedan
Jun 12, 2014·The Journal of Biological Chemistry·Kaare Bjerregaard-AndersenJ Preben Morth

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