InterPro domain: IPR016169

According to structural similarities and conserved sequence motifs,FAD-binding domains have been grouped in three main families: (i) theferredoxin reductase (FR)-type FAD-binding domain,(ii) the FAD-binding domains that adopt a Rossmann fold and (iii) the p-cresol methylhydroxylase (PCMH)-type FAD-binding domain [ 1 ].

The PCMH-type FAD-binding domain consists of two alpha-beta subdomains: one is composed of three parallel beta-strands (B1-B3) surrounded by alpha-helices, and is packed against the second subdomain containing five antiparallel beta-strands (B4-B8) surrounded by alpha-helices [ 2 ]. The two subdomains accommodate the FAD cofactor between them [ 3 ]. This superfamily represents the second (C-terminal) subdomain, which is found in:

• CO dehydrogenase flavoprotein (N-terminal domain; [ 4 ]) family, which includes xanthine oxidase (domain 3) ( 1.17.3.2 ) [ 5 ], subunit A of xanthine dehydrogenase (domain 3) ( 1.17.1.4 ) [ 6 ], medium subunit of quinoline 2-oxidoreductase (QorM) ( 1.3.99.17 ) [ 7 ], and the beta-subunit of 4-hydroxybenzoyl-CoA reductase (HrcB) (N-terminal domain) ( 1.3.99.20 ) [ 8 ].
• Uridine diphospho-N-acetylenolpyruvylglucosamine reductase (MurB) (N-terminal domain) [ 9 ].

1. Sequence-structure analysis of FAD-containing proteins. Protein Sci. 10, 1712-28
2. Structures of the flavocytochrome p-cresol methylhydroxylase and its enzyme-substrate complex: gated substrate entry and proton relays support the proposed catalytic mechanism. J. Mol. Biol. 295, 357-74
3. Flavoenzymes: diverse catalysts with recurrent features. Trends Biochem. Sci. 25, 126-32
4. The effect of intracellular molybdenum in Hydrogenophaga pseudoflava on the crystallographic structure of the seleno-molybdo-iron-sulfur flavoenzyme carbon monoxide dehydrogenase. J. Mol. Biol. 301, 1221-35
5. The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition. Proc. Natl. Acad. Sci. U.S.A. 101, 7931-6
6. Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure 10, 115-25
7. Active site geometry and substrate recognition of the molybdenum hydroxylase quinoline 2-oxidoreductase. Structure 12, 1425-35
8. Structure of a xanthine oxidase-related 4-hydroxybenzoyl-CoA reductase with an additional [4Fe-4S] cluster and an inverted electron flow. Structure 12, 2249-56
9. X-ray crystal structures of the S229A mutant and wild-type MurB in the presence of the substrate enolpyruvyl-UDP-N-acetylglucosamine at 1.8-A resolution. Biochemistry 36, 806-11