hide
Free keywords:
Methylenetetrahydromethanopterin reductase; bacterial luciferase; crystal structure; non-prolyl cis-peptide bond coenzyme F
420; FMN
Abstract:
Methylenetetratetrahydromethanopterin reductase (Mer) is involved in CO2 reduction to methane in methanogenic archaea and catalyses the reversible reduction of methylenetetrahydromethanopterin (methylene-H4MPT) to methyl-H4MPT with coenzyme F(420)H2, which is a reduced 5'-deazaflavin. Mer was recently established as a TIM barrel structure containing a nonprolyl cis-peptide bond but the binding site of the substrates remained elusive. We report here on the crystal structure of Mer in complex with F420 at 2.6 A resolution. The isoalloxazine ring is present in a pronounced butterfly conformation, being induced from the Re-face of F420 by a bulge that contains the non-prolyl cis-peptide bond. The bindingmode of F420 is very similar to that in F420-dependent alcohol dehydrogenase Adf despite the low sequence identity of 21%. Moreover, binding of F420 to the apoenzyme was only associated with minor conformational changes of the polypeptide chain. These findings allowed us to build an improved model of FMN into its binding site in bacterial luciferase, which belongs to the same structural family as Mer and Adf and also contains a nonprolyl cis-peptide bond in an equivalent position.
