PROSITE documentation PDOC51387 [for PROSITE entry PS51387]

PCMH-type FAD-binding domain profile




Description

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 [3]. 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 [4].

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>) [5]. The two subdomains accomodate the FAD cofactor between them [2]. 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 [6].

Some proteins containing a PCMH-type FAD-binding domain are listed below:

  • Bacterial UDP-N-acetylenolpyruvoylglucosamine reductase (EC 1.1.1.158). It is involved in the cell wall formation.
  • Vertebrate alkyldihydroxyacetonephosphate synthase (EC 2.5.1.26).
  • Eukaryotic lactate dehydrogenase D (EC 1.1.2.4).
  • Bacterial carbon monoxide dehydrogenase (EC 1.2.99.2). It catalyzes the oxidation of carbon monoxide to carbon dioxide.

The profile we developed covers the whole PCMH-type FAD-binding domain.

Last update:

June 2008 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

FAD_PCMH, PS51387; PCMH-type FAD-binding domain profile  (MATRIX)


References

1AuthorsMathews F.S.
TitleNew flavoenzymes.
SourceCurr. Opin. Struct. Biol. 1:954-967(1991).

2AuthorsFraaije M.W., Mattevi A.
TitleFlavoenzymes: diverse catalysts with recurrent features.
SourceTrends Biochem. Sci. 25:126-132(2000).
PubMed ID10694883

3AuthorsMattevi A.
TitleTo be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes.
SourceTrends Biochem. Sci. 31:276-283(2006).
PubMed ID16600599
DOI10.1016/j.tibs.2006.03.003

4AuthorsDym O., Eisenberg D.
TitleSequence-structure analysis of FAD-containing proteins.
SourceProtein Sci. 10:1712-1728(2001).
PubMed ID11514662

5AuthorsCunane L.M., Chen Z.W., Shamala N., Mathews F.S., Cronin C.N., McIntire W.S.
TitleStructures of the flavocytochrome p-cresol methylhydroxylase and its enzyme-substrate complex: gated substrate entry and proton relays support the proposed catalytic mechanism.
SourceJ. Mol. Biol. 295:357-374(2000).
PubMed ID10623531
DOI10.1006/jmbi.1999.3290

6AuthorsMcIntire W., Edmondson D.E., Hopper D.J., Singer T.P.
Title8 alpha-(O-Tyrosyl)flavin adenine dinucleotide, the prosthetic group of bacterial p-cresol methylhydroxylase.
SourceBiochemistry 20:3068-3075(1981).
PubMed ID7248267



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