Disease relevance of Acriflavine

• Finally, A beta-induced H2O2 production and A beta toxicity are blocked by reagents that inhibit flavin oxidases, suggesting that A beta activates a member of this class of enzymes [1].
• We have studied the mechanism of photoactivation (light-induced reduction of the flavin adenine dinucleotide cofactor) of Escherichia coli DNA photolyase using time-resolved absorption spectroscopy [2].
• Furthermore, ex vivo examination of cultures proved the presence of Helicobacter pylori and the active uptake of acriflavine into the bacteria [3].
• Photoreception in Neurospora crassa: correlation of reduced light sensitivity with flavin deficiency [4].
• The native flavin, FMN, has been removed from the l-lactate oxidase of Aerococcus viridans, and the apoprotein reconstituted with 12 FMN derivatives with various substituents at the flavin 6- and 8-positions [5].

Psychiatry related information on Acriflavine

• Exciting the semiquinone form of the flavin produces two transient EPR signals: a fast signal that is limited by the time response of the instrument and a slower signal with a lifetime of approximately 6 ms [6].

High impact information on Acriflavine

• One feature of the complex II structures is a linear electron transport chain that extends from the flavin and iron-sulfur redox cofactors in the membrane extrinsic domain to the quinone and b heme cofactors in the membrane domain [7].
• Cryptochromes are flavin-containing blue light photoreceptors related to photolyases-they are found in both plants and animals and have recently been described for bacteria [8].
• We positionally cloned FKF1, which encodes a novel protein with a PAS domain similar to the flavin-binding region of certain photoreceptors, an F box characteristic of proteins that direct ubiquitin-mediated degradation, and six kelch repeats predicted to fold into a beta propeller [9].
• Irradiation with blue light relieves this repression, presumably through an intra- or intermolecular redox reaction mediated through the flavin bound to the N-terminal photolyase-like domain [10].
• Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome [11].

Chemical compound and disease context of Acriflavine

• The flavin hydroperoxide at the active site of the mixed-function oxidase 2-aminobenzoyl-CoA monooxygenase/reductase (Azoarcus evansii) transfers an oxygen to the 5-position of the 2-aminobenzoyl-CoA substrate to provide the alkoxide intermediate II(-) [12].
• The overall structure of NfsA is similar to the NADPH-dependent flavin reductase of Vibrio harveyi, despite definite difference in the spatial arrangement of residues around the putative substrate-binding site [13].
• Escherichia coli general NAD(P)H:flavin oxidoreductase (Fre) does not have a bound flavin cofactor; its flavin substrates (riboflavin, FMN, and FAD) are believed to bind to it mainly through the isoalloxazine ring [14].
• This was demonstrated from spin trapping experiments and from the ability of the flavin reductase to achieve a superoxide dismutase (SOD)-sensitive reduction of cytochrome c. The participation of the flavin reductase to O2-. generation in E. coli cells has been studied [15].
• Interactions of pyridine nucleotides with redox forms of the flavin-containing NADH peroxidase from Streptococcus faecalis [16].

Biological context of Acriflavine

• These responses--which in higher plants include phototropism, inhibition of hypocotyl elongation, and stomatal opening--are in many cases thought to be mediated by flavin-type photoreceptors [17].
• Movement of the flavin appears to be essential for the translocation of substrates and products into the solvent-shielded active site during catalysis [18].
• Flavin-linked peroxide reductases: protein-sulfenic acids and the oxidative stress response [19].
• Mechanisms underlying the differential effects of ethanol on the bioavailability of riboflavin and flavin adenine dinucleotide [20].
• Although common flavin and NADPH-binding sites are recognizable, there is only approximately 38% amino acid sequence identity [21].

Anatomical context of Acriflavine

• The flavin adenine dinucleotide--dependent monooxygenase in mammalian hepatic microsomes plays a major role in the oxidative metabolism of thioether-containing pesticides [22].
• Cytochrome b558: the flavin-binding component of the phagocyte NADPH oxidase [23].
• Studies of acriflavine loading in normal and NPC1 fibroblasts indicated that NPC1 uses a proton motive force to remove accumulated acriflavine from the endosomal/lysosomal system [24].
• The magnitude of the cytochrome b signal in the optical spectrum of the patients' granulocytes was less than 4% of the normal value, whereas the amount of noncovalently bound flavin in these cells was normal [25].
• Is the flavin-deficient red blood cell common in Maremma, Italy, an important defense against malaria in this area [26]?

Associations of Acriflavine with other chemical compounds

• In both derivatives the nicotinamide and flavin groups associate through hydrogen bonding [27].
• Auxin biosynthesis by the YUCCA flavin monooxygenases controls the formation of floral organs and vascular tissues in Arabidopsis [28].
• The three known NOS isoforms are all dimeric, bi-domain enzymes that contain iron protoporphyrin IX, flavin adenine dinucleotide, flavin mononucleotide, and tetrahydrobiopterin as bound prosthetic groups [29].
• Sequence analysis revealed sequences compatible with binding domains for calcium/calmodulin, flavin mononucleotide, flavin adenine nucleotide and NADPH [30].
• Here we report the identification of a novel flavin adenine dinucleotide-dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine) [31].

Gene context of Acriflavine

• Phototropin 1 (phot1) is a Ser/Thr photoreceptor kinase that binds two molecules of flavin mononucleotide as its chromophores and undergoes autophosphorylation in response to blue light [32].
• In addition to its tetrapyrrole clearance role in the fetus, BVR-B has flavin and ferric reductase activities in the adult [33].
• Cryptochrome is a group of flavin-type blue light receptors that regulate plant growth and development [34].
• It is caused by loss-of-function mutations in FMO3 encoding flavin-containing mono-oxygenase 3 [35].
• Genetic evidence has confirmed that the flavin nucleotide imbalance of G178 mutants is caused by mutations in FLX1 [36].

Analytical, diagnostic and therapeutic context of Acriflavine

• Cultured bacteria were re-assessed ex vivo using confocal microscopy with and without acriflavine staining [3].
• Redox titrations and electron paramagnetic resonance spectroscopy exclude the iron-sulfur clusters and flavin radical as the source of superoxide, and, in the absence of a proton motive force, superoxide formation is not enhanced during turnover [37].
• These results and Trp-->Phe replacement by site-directed mutagenesis reveal that flavin radical photoreduction is achieved by electron abstraction from Trp-306 by the excited-state FADH0 [38].
• Exposure of photolyase on T<>T-damaged DNA films to near-UV/blue light leads to changes in the flavin signal consistent with repair, as confirmed by parallel HPLC experiments [39].
• The circular dichroism spectrum of FMN bound to luciferase has structure which correlates well with the optical absorption spectrum of the bound flavin [40].

References