title: Structural basis of the hydride transfer mechanism in F(420)-dependent methylenetetrahydromethanopterin dehydrogenase.
abstract: F(420)-dependent methylenetetrahydromethanopterin (methylene-H(4)MPT) dehydrogenase (Mtd) of Methanopyrus kandleri is an enzyme of the methanogenic energy metabolism that catalyzes the reversible hydride transfer between methenyl-H(4)MPT(+) and methylene-H(4)MPT using coenzyme F(420) as hydride carrier. We determined the structures of the Mtd-methylene-H(4)MPT, Mtd-methenyl-H(4)MPT(+), and the Mtd-methenyl-H(4)MPT(+)-F(420)H(2) complexes at 2.1, 2.0, and 1.8 A resolution, respectively. The pterin-imidazolidine-phenyl ring system is present in a new extended but not planar conformation which is virtually identical in methenyl-H(4)MPT(+) and methylene-H(4)MPT at the current resolution. Both substrates methenyl-H(4)MPT(+) and F(420)H(2) bind in a face to face arrangement to an active site cleft, thereby ensuring a direct hydride transfer between their C14a and C5 atoms, respectively. The polypeptide scaffold does not reveal any significant conformational change upon binding of the bulky substrates but in turn changes the conformations of the substrate rings either to avoid clashes between certain ring atoms or to adjust the rings involved in hydride transfer for providing an optimal catalytic efficiency.
authors.affiliation: Max-Planck-Institut fur Biophysik, Max-von-Laue-Strasse 3, D-60438 Frankfurt am Main, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ceh
authors.forename: Ulrike
authors.initials: U
authors.lastname: Demmer
authors.forename: Eberhard
authors.initials: E
authors.lastname: Warkentin
authors.forename: Johanna
authors.initials: J
authors.lastname: Moll
authors.forename: Rudolf K
authors.initials: RK
authors.lastname: Thauer
authors.forename: Seigo
authors.initials: S
authors.lastname: Shima
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ermler
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019605:Euryarchaeota / Q000201:enzymology / Q000378:metabolism; D008958:Models, Molecular; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000587:Oxidoreductases Acting on CH-NH Group Donors; C047126:methylenetetrahydromethanopterin dehydrogenase