Control of Substrate Access to the Active Site in Methane Monooxygenase
Methanotrophs consume methane as their sole carbon source and play an essential role in the global carbon cycle by limiting its atmospheric content. These bacteria oxidize methane to methanol using soluble methane monooxygenases having hydroxylase, regulatory, and reductase protein components. Until now, the catalytic mechanism has remained ambiguous due to lack of atomic-level information about component interactions. Here we report the 2.9 Å resolution crystal structure of soluble methane monooxygenase hydroxylase (MMOH) in complex with its regulatory component (MMOB) from Methylococcus capsulatus (Bath). MMOB docks in a canyon formed at the a2b2interface of the a2b2g2 MMOH dimer, and its unstructured N-terminus forms a ring-like structure on the MMOH a-subunit. These interactions control O2, methane, and proton access to the catalytic diiron center at the active site by altering the internal architecture of the a-subunits and effect conformational changes at key active site residues involved in methane oxidation.