PDBsum entry 6sek

Oxidoreductase

PDB id: 6sek

Contents

Protein chains

504 a.a.

Ligands

FAD ×2

NAP ×2

LMT

EPE ×2

GLC ×2

Waters ×27

PDB id:

6sek

Name:

Oxidoreductase

Title:

Crystal structure of ancestral flavin-containing monooxygenase (fmo) 5

Structure:

Ancestral flavin-containing monooxygenase 5. Chain: a, b. Engineered: yes

Source:

Synthetic construct. Organism_taxid: 32630. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.70Å R-factor: 0.226 R-free: 0.295

Authors:

C.Nicoll,G.Bailleul,F.Fiorentini,M.L.Mascotti,M.Fraaije,A.Mattevi

Key ref:

C.R.Nicoll et al. (2020). Ancestral-sequence reconstruction unveils the structural basis of function in mammalian FMOs. Nat Struct Mol Biol, 27, 14-24. PubMed id: 31873300 DOI: 10.1038/s41594-019-0347-2

Date:

30-Jul-19 Release date: 25-Dec-19

Protein chains

No UniProt id for this chain

Struc: 504 a.a.

DOI no: 10.1038/s41594-019-0347-2

Nat Struct Mol Biol 27:14-24 (2020)

PubMed id: 31873300

Ancestral-sequence reconstruction unveils the structural basis of function in mammalian FMOs.

C.R.Nicoll, G.Bailleul, F.Fiorentini, M.L.Mascotti, M.W.Fraaije, A.Mattevi.

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.