 |
PDBsum entry 6sek
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Oxidoreductase
|
PDB id
|
|
|
|
6sek
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Ancestral-Sequence reconstruction unveils the structural basis of function in mammalian fmos.
|
|
|
Authors
|
|
C.R.Nicoll,
G.Bailleul,
F.Fiorentini,
M.L.Mascotti,
M.W.Fraaije,
A.Mattevi.
|
|
|
Ref.
|
|
Nat Struct Mol Biol, 2020,
27,
14-24.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Flavin-containing monooxygenases (FMOs) are ubiquitous in all domains of life
and metabolize a myriad of xenobiotics, including toxins, pesticides and drugs.
However, despite their pharmacological importance, structural information
remains bereft. To further our understanding behind their biochemistry and
diversity, we used ancestral-sequence reconstruction, kinetic and
crystallographic techniques to scrutinize three ancient mammalian FMOs: AncFMO2,
AncFMO3-6 and AncFMO5. Remarkably, all AncFMOs could be crystallized and were
structurally resolved between 2.7- and 3.2-Å resolution. These crystal
structures depict the unprecedented topology of mammalian FMOs. Each employs
extensive membrane-binding features and intricate substrate-profiling tunnel
networks through a conspicuous membrane-adhering insertion. Furthermore, a
glutamate-histidine switch is speculated to induce the distinctive
Baeyer-Villiger oxidation activity of FMO5. The AncFMOs exhibited catalysis akin
to human FMOs and, with sequence identities between 82% and 92%, represent
excellent models. Our study demonstrates the power of ancestral-sequence
reconstruction as a strategy for the crystallization of proteins.
|
|
|
|
|
|
|
