Enzyme catalysis by selective compression of bulky ring-shaped substrates
The hydride transfer between methylene-tetrahydromethanopterin and NADP+
High-resolution crystal structures of tertiary methylene-tetrahydromethanopterin (H4MPT)-substrate complexes show how the substrates NADP+ and methylene-H4MPT are, at first, bound into an open catalytic cleft and then transferred into a strained but activated conformation upon cleft closure. The compressed substrate rings allow an efficient hydride transfer, which is presumably based on a hydrogen tunneling effect.
A research team from the Max Planck Institutes for Terrestrial Microbiology in Marburg and of Biophysics investigated the hydride transfer of methylene-tetrahydromethanopterin (methylene-H4MPT) to NADP+. This reaction, catalyzed by a methylene-H4MPT dehydrogenase, represents an important step in the energy metabolism of bacteria that oxidize methanol or methane to CO2. Some bacteria use the coenzyme H4MPT as a single-carbon (C1) carrier or activator, while the majority of microorganisms use tetrahydrofolate. The structures of the methylene-H4MPT dehydrogenase NADP+ methylene-/methenyl+ - H4MPT complexes from Methylorubrum extorquens were determined up to a resolution of 1.08 and 1.5 Å in an active conformation, respectively. This allowed a detailed analysis of the deformable substrate rings, their conformational changes due to the closing of the bond gaps and the transfer path of the hydride. The extremely short distance of 2.5 Å - compared to the van der Waals distance of about 3.2 Å - between the hydride-transferring nicotinamide C4 and imidazoline C14A atoms is an indicator of the imposed pressure and suggests a hydride transfer based on a hydrogen tunneling mechanism.