Structural basis for enzymatic terminal C–H bond functionalization of alkanes

Chai, Jin; Guo, Gongrui; McSweeney, Sean M.; Shanklin, John; Liu, Qun

doi:10.1038/s41594-023-00958-0

Structural basis for enzymatic terminal C–H bond functionalization of alkanes

Journal Article · Thu Mar 30 00:00:00 EDT 2023 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/s41594-023-00958-0· OSTI ID:1960267

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Brookhaven National Laboratory (BNL), Upton, NY (United States)
Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)

Alkane monooxygenase (AlkB) is a widely occurring integral membrane metalloenzyme that catalyzes the initial step in the functionalization of recalcitrant alkanes with high terminal selectivity. AlkB enables diverse microorganisms to use alkanes as their sole carbon and energy source. Here we present the 48.6-kDa cryo-electron microscopy structure of a natural fusion from Fontimonas thermophila between AlkB and its electron donor AlkG at 2.76 Å resolution. The AlkB portion contains six transmembrane helices with an alkane entry tunnel within its transmembrane domain. A dodecane substrate is oriented by hydrophobic tunnel-lining residues to present a terminal C–H bond toward a diiron active site. AlkG, an [Fe–4S] rubredoxin, docks via electrostatic interactions and sequentially transfers electrons to the diiron center. The archetypal structural complex presented reveals the basis for terminal C–H selectivity and functionalization within this broadly distributed evolutionary class of enzymes.

View Accepted Manuscript (DOE)

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC0012704

OSTI ID:: 1960267

Report Number(s):: BNL--224105-2023-JAAM

Journal Information:: Nature Structural & Molecular Biology, Journal Name: Nature Structural & Molecular Biology Journal Issue: 4 Vol. 30; ISSN 1545-9993

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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