PDBsum entry 2gv8

Oxidoreductase

PDB id: 2gv8

Contents

Protein chains

442 a.a. *

Ligands

FAD ×2

NDP ×2

GOL ×2

Waters ×432

* Residue conservation analysis

PDB id:

2gv8

Name:

Oxidoreductase

Title:

Crystal structure of flavin-containing monooxygenase (fmo) from s.Pombe and NADPH cofactor complex

Structure:

Monooxygenase. Chain: a, b. Engineered: yes

Source:

Schizosaccharomyces pombe. Fission yeast. Organism_taxid: 4896. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.232 R-free: 0.259

Authors:

S.Eswaramoorthy,S.Swaminathan,S.K.Burley,New York Sgx Research Center For Structural Genomics (Nysgxrc)

Key ref:

S.Eswaramoorthy et al. (2006). Mechanism of action of a flavin-containing monooxygenase. Proc Natl Acad Sci U S A, 103, 9832-9837. PubMed id: 16777962 DOI: 10.1073/pnas.0602398103

Date:

02-May-06 Release date: 06-Jun-06

Protein chains

Q9HFE4  (FMO1_SCHPO) -  Thiol-specific monooxygenase from Schizosaccharomyces pombe (strain 972 / ATCC 24843)

Seq: 447 a.a.

Struc: 442 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.13.- - ?????

DOI no: 10.1073/pnas.0602398103

Proc Natl Acad Sci U S A 103:9832-9837 (2006)

PubMed id: 16777962

Mechanism of action of a flavin-containing monooxygenase.

S.Eswaramoorthy, J.B.Bonanno, S.K.Burley, S.Swaminathan.

ABSTRACT

Elimination of nonnutritional and insoluble compounds is a critical task for any living organism. Flavin-containing monooxygenases (FMOs) attach an oxygen atom to the insoluble nucleophilic compounds to increase solubility and thereby increase excretion. Here we analyze the functional mechanism of FMO from Schizosaccharomyces pombe using the crystal structures of the wild type and protein-cofactor and protein-substrate complexes. The structure of the wild-type FMO revealed that the prosthetic group FAD is an integral part of the protein. FMO needs NADPH as a cofactor in addition to the prosthetic group for its catalytic activity. Structures of the protein-cofactor and protein-substrate complexes provide insights into mechanism of action. We propose that FMOs exist in the cell as a complex with a reduced form of the prosthetic group and NADPH cofactor, readying them to act on substrates. The 4alpha-hydroperoxyflavin form of the prosthetic group represents a transient intermediate of the monooxygenation process. The oxygenated and reduced forms of the prosthetic group help stabilize interactions with cofactor and substrate alternately to permit continuous enzyme turnover.

Selected figure(s)

Figure 2.
Fig. 2. Ribbon representation of the protein and ball-and-stick model of FAD. The strand–turn–helix motifs and the loop interlinking the two domains are labeled. FAD is in the large domain and has no interaction with the small domain.

Figure 4.
Fig. 4. Schematic representation of the functional mechanism of FMO. Only the relevant parts required to explain the function, isoalloxazine, nicotinamide, and methimazole, are shown. Step 1 is seen in the wild type, step 3 is seen in the protein–cofactor complex, and step 5 is seen in the protein–methimazole complex structures.

Figures were selected by an automated process.