Ferritins are an ancient superfamily of protein nanocages that synthesize, reversibly, iron concentrates for cellular use, heme, FeS cluster, and Fe-protein synthesis and provide oxidant protection by consumption of dioxygen or hydrogen peroxide and ferrous iron during stress; the protein cavities containing the minerals are ϳ60% of the cage volume (1-4). Ferritins differ in cage size, location, and mechanism of catalytic sites, mineral size, and mineral crystallinity; the Fe 2ϩ /O 2 oxidoreductase sites are also called ferroxidase sites or FC (ferroxidase centers) sites (1-5). In eukaryotic H ferritins, Fe 2ϩ and dioxygen are substrates for oxidoreductase sites and are catalytically coupled at multiple protein sites to synthesize diferric oxo mineral precursors (Fig. 1). Consumption of both iron and oxygen by ferritins accounts for the antioxidant response and iron-controlled gene regulation of ferritins in eukaryotes (6). Many catalytic proteins use iron and oxygen to produce a variety of organic products. Such products include unsaturated fatty acids such as oleate stearoyl-CoA desaturase-1 (7), deoxyribose (ribonucleotide reductase), and prolyhydroxyl modification of oxygen-sensing DNA transcription factors, e.g. hypoxia-inducible factor-␣ (8). Only in ferritins are both substrates inorganic. The exclusive use of inorganic substrates may relate to the ancient origins of the ferritins, which are distributed in all kingdoms and in both anaerobes and aerobes; ferritin gene deletion is lethal early in mammalian embryogenesis (9).There are two types of protein channels that move iron into and through the 24 subunit cages during synthesis of [Fe 3ϩ O] n in eukaryotic ferritins. The two functional types of ferritin channels are: (i) ion entry channels around the 3-fold axes, for , where diferric oxo mineral precursors produced by oxidoreduction fuse to tetramers and larger multimers before exiting from the protein cage for mineral growth.Recent high resolution structural studies show that ferritin is a soluble ion channel protein with lines of multiple metal ions (10), much like K ϩ and other membrane ion channel proteins. The eight Fe 2ϩ entry channels (Fig. 1) suggest roles beyond just electrostatics for the conserved carboxylates, such as ion selectivity at the channel constriction or directing Fe 2ϩ substrate ions to active sites in three subunits that also form the entry channels (10). The Fe 3ϩ O nucleation channels were recently identified using 13 C-13 C solution NMR spectroscopy in the presence and absence of Fe 3ϩ , by the disappearance of resonances within 5 Å of Fe 3ϩ O moving away from the active sites (11). Nucleation channel exits into the cavity are clustered around the 4-fold axes of the cage, which facilitates ordered mineral growth. 4 The abbreviations used are: DFP, diferric peroxo; MCD, magnetic circular dichroism; bis-Tris, bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane.
Molybdenum and tungsten have similar ionic radii and chemical properties. Tungsten is the heaviest atom and the only third-row transition element that exhibits biological activity in enzymes. Molybdenum is the only second-row transition metal that exhibits biological activity when it is present in a cofactor of a metalloenzyme. Both metals are present mainly in enzymes that catalyze oxygen atom transfer reactions. In these enzymes they are coordinated by the two dithiolene sulfur atoms of a pterin molecule, called a molybdopterin cofactor (25). In the case of tungsten, the metal is always coordinated by two pterin moieties, forming a so called bis-pterin cofactor (9, 13). Molybdenum is an essential trace metal for many forms of life whereas tungsten is found mostly in archaea and in some bacteria. The molybdenum cofactor-containing enzymes can be divided into three families depending on the coordination chemistry of the Mo ligand: the sulfite oxidases; the xanthine oxidoreductases, also including the aldehyde oxidases; and the dimethyl sulfoxide reductases, which are found only in prokaryotes (18, 35). The tungsten cofactor-containing enzymes consist only of the aldehyde oxidoreductases (AORs), formate dehydrogenases (FDHs), and an acetylene hydratase (13). Based on sequence comparison the FDHs and acetylene hydratase are part of the molybdenum-containing dimethyl sulfoxide reductase family.The transport of molybdate has been well characterized in particular for Escherichia coli, which expresses a high-affinity ABC transporter for molybdate encoded by the modABC genes (27). The periplasmic molybdate binding protein ModA binds specifically molybdate and tungstate and not sulfate or other anions (27). Crystal structures of the E. coli and the Azotobacter vinelandii ModA indicate that the specificity for molybdate and tungstate is mostly determined by the size of the binding pocket. The Cambridge Structural Database (2) gives 1.75 Ϯ 0.04 Å and 1.76 Ϯ 0.02 Å for molybdate and tungstate, respectively, and 1.47 Ϯ 0.02 Å for sulfate. The ModA proteins cannot discriminate between molybdate and tungstate. The first tungsten-specific ABC transporter was identified in Eubacterium acidaminophilum (17). The periplasmic tungsten uptake protein (TupA) was cloned and expressed in E. coli and was shown to bind only tungstate with a high affinity. A crystal structure of TupA is not yet available, and it is not clear what the structural basis is of the specificity for tungstate over molybdate. Recently, a high-affinity vanadate transporter, which was highly selective for vanadate compared to tungstate, was identified in the cyanobacterium Anabaena variabilis ATCC 29413 based on the sequence similarity with the TupA protein from E. acidaminophilum (58% sequence similarity) (24). A. variabilis ATCC 29413 expresses an alternative V-dependent nitrogenase for the fixation of nitrogen, and therefore it requires vanadate (24). The specificity of this transporter for vanadate indicates that high sequence similarities are not conclusive fo...
The hydration of oleic acid into 10-hydroxystearic acid was originally described for a Pseudomonas cell extract almost half a century ago. In the intervening years, the enzyme has never been characterized in any detail. We report here the isolation and characterization of oleate hydratase (EC 4.2.1.53) from Elizabethkingia meningoseptica.
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