Proteins heme activator protein

Hapl (heme activator protein 1) is a heme-regulated transcription factor found in S, cerevisiae (48), and we hypothesized that this protein might play a role in the regulation of HAS transcription. Consistent with this hypothesis, the... 

In addition to intracellular heme-containing proteins, big-conductance calcium-dependent K+ (BKCa) channels and calcium-spark activated transient Kca channels in plasma membrane are also tar geted by CO [3]. As well known, nitric oxide (NO) also activates BKca channels in vascular smooth muscle cells. While both NO and CO open BKCa channels, CO mainly acts on alpha subunit of BKCa channels and NO mainly acts on beta subunit of BKca channels in vascular smooth muscle cells. Rather than a redundant machinery, CO and NO provide a coordinated regulation of BKca channel function by acting on different subunits of the same protein complex. Furthermore, pretreatment of vascular smooth muscle... 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Loew GH, Harris DL. 2000. Role of the heme active site and protein environment in structure, spectra and function of the cytochrome P450s. Chem Rev 100 407. 

The improvement of its activity and stability has been approach by the use of GE tools (see Refs. [398] and [399], respectively). A process drawback is the fact that the oxidation of hydrophobic compounds in an organic solvent becomes limited by substrate partition between the active site of the enzyme and the bulk solvent [398], To provide the biocatalyst soluble with a hydrophobic active site access, keeping its solubility in organic solvents, a double chemical modification on horse heart cytochrome c has been performed [400,401], First, to increase the active-site hydrophobicity, a methyl esterification on the heme propionates was performed. Then, polyethylene glycol (PEG) was used for a surface modification of the protein, yielding a protein-polymer conjugates that are soluble in organic solvents. 

Hemoglobin is another heme-containing protein, which has been shown to be active towards PAH, oxidation in presence of peroxide [420], This protein was also modified via PEG and methyl esterification to obtain a more hydrophobic protein with altered activity and substrate specificity. The modified protein had four times the catalytic efficiency than that of the unmodified protein for pyrene oxidation. Several PAHs were also oxidized including acenaphthene, anthracene, azulene, benzo(a)pyrene, fluoranthene, fluorene, and phenanthrene however, no reaction was observed with chrysene and biphenyl. Modification of hemoglobin with p-nitrophenol and p-aminophenol has also been reported [425], The modification was reported to enhance the substrate affinity up to 30 times. Additionally, the solvent concentration at which the enzyme showed maximum activity was also higher. Both the effects were attributed to the increase in hydrophobicity of the active site. 

Cyt c is one of most important and extensively studied electron-transfer proteins, partly because of its high solubility in water compared with other redox-active proteins. In vivo, cyt c transfers an electron from complex III to complex IV, membrane-bound components of the mitochondrial electron-transfer chain. The electrochemical interrogation of cyt c has, however, been hindered because the redox-active heme center is... 

It has been said above that cyt c was one of the most important and extensively studied electron-transfer proteins with active heme centers. Thus, cyt c was widely used in enzyme-based biosensors and to study the mechanism of the catalytic process between redox enzyme and substrate. 

The enzyme catalyzing the formation of retinal 2 by means of central cleavage of P-carotene 1 has been known to exist in many tissues for quite some time. Only recently, however, the active protein was identified in chicken intestinal mucosa (3) following an improvement of a novel isolation and purification protocol and was cloned in Escherichia coli and BHK cells (4,5). Iron was identified as the only metal ion associated with the (overexpressed) protein in a 1 1 stoichiometry and since a chromophore is absent in the protein heme coordination and/or iron complexation by tyrosine can be excluded. The structure of the catalytic center remains to be elucidated by X-ray crystallography but from the information available it was predicted that the active site contains a mononuclear iron complex presumably consisting of histidine residues. This suggestion has been confirmed by... 

Myoglobin in many respects is the prototypical example of the larger family of heme containing proteins and enzymes that vary in function from the relatively simple process of reversible binding of an electron to the activation of dioxygen for substrate hydroxylation. The relationship between members of this family of proteins is not based simply on structural similarities but on similarities in chemical reactivity as well. As the structure of myoglobin is relatively simple compared to other heme proteins and as it was the first for which the three-dimensional... 

Heme alone can reportedly elicit a catalatic reaction (the reaction mediated by catalase) but at a much reduced, almost negligible, rate compared to the catalatic proteins containing heme, and this may explain the observation of catalase activity in enzymes not normally associated with catalatic activity (4, 5). Other enz5unes have evolved that can catalyze a similar reaction in the absence of heme, but this review will limit itself to a consideration of heme containing proteins with catalatic activity. 

Several heme-containing proteins, including most peroxidases 12), have been observed to exhibit a low level of catalatic activity, with the chloroperoxidase from Caldariomyces fumago exhibiting the greatest reactivity as a catalase (13-15). Despite the fact that there is as yet only one such example to consider, it provides an alternate mechanism for the catalatic reaction and is addressed in this review. It was first characterized for its ability to chlorinate organic substrates in the presence of chloride and hydrogen peroxide at acid pH, but was later found... 

Other proteins such as methemoglobin and metmyoglobin have been observed to produce molecular oxygen in the presence of hydrogen peroxide, but at a very low rate (5). This may simply be a property of the heme, which can promote a low-level catalatic reaction in the absence of protein. Consequently, it is possible that all heme-containing proteins may exhibit catalatic reactions if assayed carefully, but such minor, largely nonquantifiable activities are not considered here. 

Several models have been proposed for the active center of iron and sulphur in Clostridial ferredoxin in which the cysteine residues in the peptide chain participate in the sulphur bridging. Fig 9 166). Unfortunately X-ray analysis of crystals of these proteins has not been completed. It is difficult to confirm that all the irons are clustered in a single linear array 167, 168). X-ray studies of another non-heme iron protein, the high potential iron protein, hipip, from chromatium, carried out by J. Kraut (personal communication), indicate that the four irons of this molecule may be clustered in a tetrahedral array. 

Mansuy, D. Battioni, P. Diversity of reactions catalyzed by heme-thiolate proteins, The Porphyrin Handbook. Volume 4. Biochemistry and Binding Activation of Small Molecules Eds. Kadish, . M. Smith, . M. Guilard, R. Academic Press San Diego, 2000, pp. 1-15. 

Carboxylic groups of the protoporphyrin IX ligand (Scheme 10) are phenomenal candidates for the targeted active-site modification of HRP and other heme-containing proteins. There is a clear parallel with the active site modification of GO (Section IV.A.2). The modification of hemin chloride by H2NCH2Fc in the presence of EDC and V-hydroxysuccinimide in DMF affording mono- and bis-amidated propionic acid residues is shown in Scheme 10 (144). The Fc Heme is actually a mixture of two diastereomers. -HRP has been prepared according to an acidic methyl ethyl ketone procedure of Teale (145)... 

A dipeptide Met- , derived from sardine muscle (Matsufuji et ah, 1994), stimulates expression of the antioxidant defense protein HO-1 in a concentration-dependent manner. Previous findings revealed that HO-1 protein expression is accompanied by the induction of a secondary antioxidant protein, ferritin. In a present study, the effect of Met- on the expression of the antioxidant stress proteins, heme oxygenase-1 (HO-1), and ferritin in endothelial cells derived from the human umbilical vein and their contribution to the decrease in radical formation that occurs under the influence of this dipeptide were studied and reported potential activity (Erdmann et ah, 2006). 

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