|PROSITE documentation PDOC51387|
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 (see <PDOC51384>), (ii) the FAD-binding domains that adopt a Rossmann fold and (iii) the p-cresol methylhydroxylase (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 PCMH-type FAD-binding domain consists of two α-β subdomains: one is composed of three parallel β-strands (B1-B3) surrounded by α-helices, and is packed against the second subdomain containing five antiparallel β-strands (B4-B8) surrounded by α-helices (see <PDB:1DII>) . The two subdomains accomodate the FAD cofactor between them . In the PCMH proteins the coenzyme FAD is also covalently attached to a tyrosine located outside the FAD-binding domain in the C-terminal catalytic domain .
Some proteins containing a PCMH-type FAD-binding domain are listed below:
The profile we developed covers the whole PCMH-type FAD-binding domain.Last update:
June 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||Cunane L.M. Chen Z.W. Shamala N. Mathews F.S. Cronin C.N. McIntire W.S.|
|Title||Structures of the flavocytochrome p-cresol methylhydroxylase and its enzyme-substrate complex: gated substrate entry and proton relays support the proposed catalytic mechanism.|
|Source||J. Mol. Biol. 295:357-374(2000).|
|6||Authors||McIntire W. Edmondson D.E. Hopper D.J. Singer T.P.|
|Title||8 alpha-(O-Tyrosyl)flavin adenine dinucleotide, the prosthetic group of bacterial p-cresol methylhydroxylase.|