The quest for the particulate methane monooxygenase active site

Particulate methane monooxygenase is a copper-containing, membrane-bound metalloenzyme that converts methane to methanol in Nature. How pMMO accomplishes this difficult reaction under ambient conditions is one of the major unsolved problems in bioinorganic chemistry. Despite considerable research efforts in the past 20 years, the active site of the enzyme remains unknown. We recently solved the first crystal structure of pMMO to 2.8 e resolution, revealing the overall structure, oligomerization state, subunit ratio, and composition and location of the metal centers. Almost none of the key structural features were predicted. In this Perspective, we review the state of knowledge before and after the structure determination, emphasizing elucidation of the pMMO active site.