Article
- The EMBO Journal (2001) 20, 6561 - 6569
- doi:10.1093/emboj/20.23.6561
Structures of F420H2:NADP+ oxidoreductase with and without its substrates bound
Eberhard Warkentin1, Björn Mamat1,2, Melanie Sordel-Klippert2, Michaela Wicke2, Rudolf K. Thauer2, Momi Iwata3, So Iwata3, Ulrich Ermler1 and Seigo Shima2
- Max-Planck-Institut für Biophysik, Heinrich-Hoffmann-Strasse 7, D-60596 Frankfurt/Main, Germany
- Max-Planck-Institut für terrestrische Mikrobiologie and Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps-Universität, Karl-von-Frisch-Strasse, D-35043 Marburg, Germany
- Department of Biological Sciences and Division of Biomedical Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK
Correspondence to:
So Iwata, E-mail: s.iwata@ic.ac.uk
Ulrich Ermler, E-mail: ulrich.ermler@mpibp-frankfurt.mpg.de
Seigo Shima, E-mail: shima@mailer.uni-marburg.de
Received 18 July 2001; Accepted 18 October 2001; Revised 2 October 2001
Abstract
Cofactor F420 is a 5'-deazaflavin derivative first discovered in methanogenic archaea but later found also to be present in some bacteria. As a coenzyme, it is involved in hydride transfer reactions and as a prosthetic group in the DNA photolyase reaction. We report here for the first time on the crystal structure of an F420-dependent oxidoreductase bound with F420. The structure of F420H2:NADP+ oxidoreductase resolved to 1.65 Å contains two domains: an N-terminal domain characteristic of a dinucleotide-binding Rossmann fold and a smaller C-terminal domain. The nicotinamide and the deazaflavin part of the two coenzymes are bound in the cleft between the domains such that the Si-faces of both face each other at a distance of 3.1 Å, which is optimal for hydride transfer. Comparison of the structures bound with and without substrates reveals that of the two substrates NADP has to bind first, the binding being associated with an induced fit.
Keywords:
- crystal structure,
- drug design,
- F420,
- hydride transfer,
- oxidoreductase
