|PROSITE documentation PDOC51384 [for PROSITE entry PS51384]|
Flavoenzymes have the ability to catalyse a wide range of biochemical reactions. They are involved in the dehydrogenation of a variety of metabolites, in electron transfer from and to redox centres, in light emission, in the activation of oxygen for oxidation and hydroxylation reactions [1,2]. About 1% of all eukaryotic and prokaryotic proteins are predicted to encode a flavin adenine dinucleotide (FAD)-binding domain . According to structural similarities and conserved sequence motifs, FAD-binding domains have been grouped in three main families: (i) the ferredoxin reductase (FR)-type FAD-binding domain, (ii) the FAD-binding domains that adopt a Rossmann fold and (iii) the PCMH-type FAD-binding domain .
The FAD cofactor consists of adenosine monophosphate (AMP) linked to flavin mononucleotide (FMN) by a pyrophosphate bond. The AMP moiety is composed of the adenine ring bonded to a ribose that is linked to a phosphate group. The FMN moiety is composed of the isoalloxazine-flavin ring linked to a ribitol, which is connected to a phosphate group. The flavin functions mainly in a redox capacity, being able to take up two electrons from one substrate and release them two at a time to a substrate or coenzyme, or one at a time to an electron acceptor. The catalytic function of the FAD is concentrated in the isoalloxazine ring, whereas the ribityl phosphate and the AMP moiety mainly stabilize cofactor binding to protein residues [1,2].
The structural core of all FR family members is well conserved. The FAD-binding fold characteristic of the FR family is a cylindrical β-domain with a flattened six-stranded antiparallel β-barrel organized into two orthogonal sheets (B1-B2-B5 and B4-B3-B6) separated by one α-helix (see for example <PDB:IA8P>) . The cylinder is open between strands B4 and B5 which makes space for the isoalloxazine and ribityl moieties of the FAD. One end of the cylinder is covered by the only helix of the domain, which is essential for the binding of the pyrophosphate groups of the FAD. The FR family contains two conserved motifs, one (R-x-Y-[ST]) located in B4 where the invariant positively charge Arg residue forms hydrogen bonds to the negative pyrophosphate oxygen atom. The other conserved sequence motif is G-x(2)-[ST]-x(2)-L-x(5)-G-x(7)-P-x-G, which is part of H1-B6 and is known as the phosphate-binding motif [4,5].
Some proteins known to contain a FR-type FAD-binding domain are listed below:
The profile we developed covers the whole ferredoxin reductase type FAD-binding domain.Note:
In addition to the FAD-binding domain, all of the FR family members have an NAD(P)H-binding domain.Last update:
May 2008 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|Source||Curr. Opin. Struct. Biol. 1:954-967(1991).|
|2||Authors||Fraaije M.W. Mattevi A.|
|Title||Flavoenzymes: diverse catalysts with recurrent features.|
|Source||Trends Biochem. Sci. 25:126-132(2000).|
|Title||To be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes.|
|Source||Trends Biochem. Sci. 31:276-283(2006).|
|4||Authors||Dym O. Eisenberg D.|
|Title||Sequence-structure analysis of FAD-containing proteins.|
|Source||Protein Sci. 10:1712-1728(2001).|
|5||Authors||Sridhar Prasad G. Kresge N. Muhlberg A.B. Shaw A. Jung Y.S. Burgess B.K. Stout C.D.|
|Title||The crystal structure of NADPH:ferredoxin reductase from Azotobacter vinelandii.|
|Source||Protein Sci. 7:2541-2549(1998).|