4GAM

Complex structure of Methane monooxygenase hydroxylase and regulatory subunit

Summary for 4GAM

• Entry DOI: 10.2210/pdb4gam/pdb
• Related: 1CKV 1MMO
• Descriptor: Methane monooxygenase component A beta chain, Methane monooxygenase component A alpha chain, Methane monooxygenase component A gamma chain, ... (6 entities in total)
• Functional Keywords: methane monooxygenase, hydroxylase, regulatory subunit b, oxidoreductase
• Biological source: Methylococcus capsulatus; More
• Total number of polymer chains: 16
• Total formula weight: 567572.36

Authors

Lee, S.J.,Lippard, S.J.,Cho, U.-S. (deposition date: 2012-07-25, release date: 2013-02-06, Last modification date: 2023-09-13)

Primary citation

Lee, S.J.,McCormick, M.S.,Lippard, S.J.,Cho, U.S.
Control of substrate access to the active site in methane monooxygenase.
Nature, 494:380-384, 2013

PubMed Abstract: Methanotrophs consume methane as their major carbon source and have an essential role in the global carbon cycle by limiting escape of this greenhouse gas to the atmosphere. These bacteria oxidize methane to methanol by soluble and particulate methane monooxygenases (MMOs). Soluble MMO contains three protein components, a 251-kilodalton hydroxylase (MMOH), a 38.6-kilodalton reductase (MMOR), and a 15.9-kilodalton regulatory protein (MMOB), required to couple electron consumption with substrate hydroxylation at the catalytic diiron centre of MMOH. Until now, the role of MMOB has remained ambiguous owing to a lack of atomic-level information about the MMOH-MMOB (hereafter termed H-B) complex. Here we remedy this deficiency by providing a crystal structure of H-B, which reveals the manner by which MMOB controls the conformation of residues in MMOH crucial for substrate access to the active site. MMOB docks at the α(2)β(2) interface of α(2)β(2)γ(2) MMOH, and triggers simultaneous conformational changes in the α-subunit that modulate oxygen and methane access as well as proton delivery to the diiron centre. Without such careful control by MMOB of these substrate routes to the diiron active site, the enzyme operates as an NADH oxidase rather than a monooxygenase. Biological catalysis involving small substrates is often accomplished in nature by large proteins and protein complexes. The structure presented in this work provides an elegant example of this principle.

PubMed: 23395959
DOI: 10.1038/nature11880

Experimental method

X-RAY DIFFRACTION (2.902 Å)