Genomes and Genes
oxidoreductases acting on ch nh group donors
Summary: Enzymes catalyzing the dehydrogenation of secondary amines, introducing a C=N double bond as the primary reaction. In some cases this is later hydrolyzed.
- Vogel M, Lawson M, Sippl W, Conrad U, Roos W. Structure and mechanism of sanguinarine reductase, an enzyme of alkaloid detoxification. J Biol Chem. 2010;285:18397-406 pubmed publisher..It appears that relatively few innovations were required to generate this selective catalyst for alkaloid detoxication, notably an insertion of 13 amino acids and the generation of a novel catalytic triad of Cys-Asp-His were sufficient...
- Pang J, Scrutton N, de Visser S, Sutcliffe M. New insights into the multi-step reaction pathway of the reductive half-reaction catalysed by aromatic amine dehydrogenase: a QM/MM study. Chem Commun (Camb). 2010;46:3104-6 pubmed publisher..This atomistic picture of the reaction sequence--including short-lived reaction intermediates and a stepwise reaction mechanism--bridges the gap between a small number of crystallographic snapshots. ..
- Jensen L, Sanishvili R, Davidson V, Wilmot C. In crystallo posttranslational modification within a MauG/pre-methylamine dehydrogenase complex. Science. 2010;327:1392-4 pubmed publisher..In addition, one of the hemes has an atypical His-Tyr axial ligation. The crystalline protein complex is catalytically competent; upon addition of hydrogen peroxide, MauG-dependent TTQ synthesis occurs...
- Goldman A, Leigh J, Samudrala R. Comprehensive computational analysis of Hmd enzymes and paralogs in methanogenic Archaea. BMC Evol Biol. 2009;9:199 pubmed publisher..This work also represents a novel approach to protein function prediction in which multiple computational methods are integrated to achieve a detailed characterization of proteins that are not well understood. ..
- Lee J, Lee S, Bae W, Lee Y, Park J, Lee S, et al. N(1)-guanyl-1,7,-diamineoheptane, an inhibitor of deoxyhypusine synthase, suppresses differentiation and induces apoptosis via mitochondrial and AMPK pathways in immortalized and malignant human oral keratinocytes. J Oral Pathol Med. 2009;38:792-800 pubmed publisher..On the basis of these observations, we propose that a strategy combining GC7 and AMPK inhibition could be developed into a novel chemotherapeutic modality in oral cancer. ..
- Kaitaniemi S, Elovaara H, Grön K, Kidron H, Liukkonen J, Salminen T, et al. The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase. Cell Mol Life Sci. 2009;66:2743-57 pubmed publisher..Characterization of AOC2 will help in evaluating the contribution of this enzyme to the pathological processes attributed to the SSAO activity and in designing specific inhibitors for the individual members of the SSAO family...
- Han Y, Ren Y, Cao C, Ren D, Zhou Y, Wang Y. Highly expressed N1-acetylpolyamine oxidase detoxifies polyamine analogue N1-cyclopropylmethyl-N11-ethylnorspermine in human lung cancer cell line A549. Chin Med J (Engl). 2009;122:1394-9 pubmed..High expression of APAO can greatly decrease the sensitivity of tumor cells to the specific polyamine analogues by detoxifying those analogues and prevent analogue induced apoptosis. ..
- Carew J, Nawrocki S, REDDY V, Bush D, Rehg J, Goodwin A, et al. The novel polyamine analogue CGC-11093 enhances the antimyeloma activity of bortezomib. Cancer Res. 2008;68:4783-90 pubmed publisher..These findings support the study of the use of the combination of bortezomib and CGC-11093 in MM patients that fail to respond to frontline therapy. ..
- Yang Y, Yuan S, Chen T, Ma P, Shang G, Dai Y. Cloning, heterologous expression, and functional characterization of the nicotinate dehydrogenase gene from Pseudomonas putida KT2440. Biodegradation. 2009;20:541-9 pubmed publisher..entomophila L48 to hydroxylate nicotinate. Gene knockout and recovery studies further confirmed the ndhSL function. ..
- Lee J, Sperandio V, Frantz D, Longgood J, Camilli A, Phillips M, et al. An alternative polyamine biosynthetic pathway is widespread in bacteria and essential for biofilm formation in Vibrio cholerae. J Biol Chem. 2009;284:9899-907 pubmed publisher..cholerae infection. Notably, the alternative polyamine biosynthetic pathway is widespread in bacteria and is likely to play a previously unrecognized role in the biology of these organisms. ..
- Yang Y, Chen T, Ma P, Shang G, Dai Y, Yuan S. Cloning, expression and functional analysis of nicotinate dehydrogenase gene cluster from Comamonas testosteroni JA1 that can hydroxylate 3-cyanopyridine. Biodegradation. 2010;21:593-602 pubmed publisher..The subunits swap results indicate the [2Fe2S] motif determines the 3-cyanopyridine hydroxylation ability, which is evidently different from the previous belief that the Mo motif determines substrate specificity. ..
- Henderson Pozzi M, Gawandi V, Fitzpatrick P. pH dependence of a mammalian polyamine oxidase: insights into substrate specificity and the role of lysine 315. Biochemistry. 2009;48:1508-16 pubmed publisher..8. These results rule out Lys315 as a source of a pK(a) in the k(cat)/K(amine) or k(cat)/k(red) profiles. They also establish that this residue does not play a critical role in amine oxidation by PAO. ..
- Adachi M, Juarez P, Fitzpatrick P. Mechanistic studies of human spermine oxidase: kinetic mechanism and pH effects. Biochemistry. 2010;49:386-92 pubmed publisher..4 in the active site are preferred for binding. ..
- Zahedi K, Huttinger F, Morrison R, Murray Stewart T, Casero R, Strauss K. Polyamine catabolism is enhanced after traumatic brain injury. J Neurotrauma. 2010;27:515-25 pubmed publisher..The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies. ..
- Tsutsumi M, Tsuse N, Fujieda N, Kano K. Site-directed mutation at residues near the catalytic site of histamine dehydrogenase from Nocardioides simplex and its effects on substrate inhibition. J Biochem. 2010;147:257-64 pubmed publisher..However, destabilization of the semiquinone form leads to kinetic hindrance due to the uphill single electron transfer from the fully reduced CFMN to the [4Fe-4S] cluster...
- Moschou P, Sarris P, Skandalis N, Andriopoulou A, Paschalidis K, Panopoulos N, et al. Engineered polyamine catabolism preinduces tolerance of tobacco to bacteria and oomycetes. Plant Physiol. 2009;149:1970-81 pubmed publisher..This strategy presents a novel approach for producing transgenic plants resistant to a broad spectrum of plant pathogens. ..
- Henderson Pozzi M, Fitzpatrick P. A lysine conserved in the monoamine oxidase family is involved in oxidation of the reduced flavin in mouse polyamine oxidase. Arch Biochem Biophys. 2010;498:83-8 pubmed publisher..In the mutant enzyme the lysine amine would be replaced by a water chain. ..
- Wilmot C, Davidson V. Uncovering novel biochemistry in the mechanism of tryptophan tryptophylquinone cofactor biosynthesis. Curr Opin Chem Biol. 2009;13:469-74 pubmed publisher..This high-valent diheme species is an alternative to Compound I, an Fe(IV)=O heme with a porphyrin or amino acid cation radical, which is typically the reactive intermediate of heme-dependent oxygenases and peroxidases. ..
- Wen B, Dai T, Li W, Zhao Y, Liu S, Zhang C, et al. Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations. J Neurol Neurosurg Psychiatry. 2010;81:231-6 pubmed publisher..The research findings suggest that the majority of Chinese patients with RR-LSM are caused by a mild type of MADD with unique myopathy which is due to ETFDH gene mutation. ..
- Pozzi M, Gawandi V, Fitzpatrick P. Mechanistic studies of para-substituted N,N'-dibenzyl-1,4-diaminobutanes as substrates for a mammalian polyamine oxidase. Biochemistry. 2009;48:12305-13 pubmed publisher..59 at pH 8.6 and -0.09 at pH 6.6. These results are consistent with direct transfer of a hydride from the neutral CN bond of the substrate to the flavin as the mechanism of polyamine oxidase. ..
- Abdelhady M, Beuerle T, Ober D. Homospermidine in transgenic tobacco results in considerably reduced spermidine levels but is not converted to pyrrolizidine alkaloid precursors. Plant Mol Biol. 2009;71:145-55 pubmed publisher..These results are discussed with respect to current models of pathway evolution. ..
- Song Y, Selak M, Watson C, Coutts C, Scherer P, Panzer J, et al. Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD). PLoS ONE. 2009;4:e8329 pubmed publisher..These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention. ..
- Takao K, Sugita Y, Shirahata A. Assay of N1-acetylpolyamine oxidase activity with N1,N11-didansylnorspermine as the substrate by ion-pair reversed phase high performance liquid chromatography. Biol Pharm Bull. 2010;33:1089-94 pubmed..This HPLC method is a rapid, sensitive and useful assay for the measurement of PAO activity. ..
- Strickland K, Hoeferlin L, Oleinik N, Krupenko N, Krupenko S. Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 2010;285:1627-33 pubmed publisher..Our study identifies human PPT as the FDH-modifying enzyme and supports the hypothesis that mammals utilize a single enzyme for all phosphopantetheinylation reactions. ..
- Fu R, Liu F, Davidson V, Liu A. Heme iron nitrosyl complex of MauG reveals an efficient redox equilibrium between hemes with only one heme exclusively binding exogenous ligands. Biochemistry. 2009;48:11603-5 pubmed publisher..The results also illustrate the electronic communication between the two iron centers, which function as a diheme unit rather than independent heme cofactors. ..
- Tang D, Dong S, Ma N, Xie D, Chen L, Fu L, et al. Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma. Hepatology. 2010;51:1255-63 pubmed publisher..EIF5A2 plays an important role in HCC invasion and metastasis by inducing EMT, as well as stimulating cytoskeleton rearrangement through activation of RhoA and Rac1. ..
- Chew D, Mah A, Baillie D. Characterizing the transcriptional regulation of let-721, a Caenorhabditis elegans homolog of human electron flavoprotein dehydrogenase. Mol Genet Genomics. 2009;282:555-70 pubmed publisher..Taken together, we find that LET-721 is a mitochondrially expressed protein that is under complex transcriptional controls. ..
- Yoda H, Fujimura K, Takahashi H, Munemura I, Uchimiya H, Sano H. Polyamines as a common source of hydrogen peroxide in host- and nonhost hypersensitive response during pathogen infection. Plant Mol Biol. 2009;70:103-12 pubmed publisher..Our present observations thus suggested that polyamines are commonly utilized as the source of hydrogen peroxide during host- and nonhost HRs in higher plants. ..
- Wagener N, Pierik A, Ibdah A, Hille R, Dobbek H. The Mo-Se active site of nicotinate dehydrogenase. Proc Natl Acad Sci U S A. 2009;106:11055-60 pubmed publisher..The MoO(OH)Se active site of NDH shows a novel type of utilization and reactivity of selenium in nature. ..
- Ishii K, Komaki H, Ohkuma A, Nishino I, Nonaka I, Sasaki M. Central nervous system and muscle involvement in an adolescent patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Brain Dev. 2010;32:669-72 pubmed publisher..Early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD. ..
- Nurhayati N, Gond D, Ober D. Evolution of pyrrolizidine alkaloids in Phalaenopsis orchids and other monocotyledons: identification of deoxyhypusine synthase, homospermidine synthase and related pseudogenes. Phytochemistry. 2009;70:508-16 pubmed publisher..This result is discussed with respect to the recent discovery of structural related PAs within grasses...
- Pledgie Tracy A, Billam M, Hacker A, Sobolewski M, Woster P, Zhang Z, et al. The role of the polyamine catabolic enzymes SSAT and SMO in the synergistic effects of standard chemotherapeutic agents with a polyamine analogue in human breast cancer cell lines. Cancer Chemother Pharmacol. 2010;65:1067-81 pubmed publisher
- Xue B, Zhang A, Jiang M. Involvement of polyamine oxidase in abscisic acid-induced cytosolic antioxidant defense in leaves of maize. J Integr Plant Biol. 2009;51:225-34 pubmed publisher..These results suggest that MPAO contributes to ABA-induced cytosolic antioxidant defense through H2O2, a Spd catabolic product...
- Seifert E, Estey C, Xuan J, Harper M. Electron transport chain-dependent and -independent mechanisms of mitochondrial H2O2 emission during long-chain fatty acid oxidation. J Biol Chem. 2010;285:5748-58 pubmed publisher..Finally, ROS production was sensitive to matrix levels of LCFA catabolic intermediates, indicating that mitochondrial export of LCFA catabolic intermediates can play a role in determining ROS levels...
- Plese B, Schröder H, Grebenjuk V, Wegener G, Brandt D, Natalio F, et al. Strombine dehydrogenase in the demosponge Suberites domuncula: characterization and kinetic properties of the enzyme crucial for anaerobic metabolism. Comp Biochem Physiol B Biochem Mol Biol. 2009;154:102-7 pubmed publisher..It is concluded that the dimer (75 kDa) has a novel structure, distinguishing it from other known marine invertebrate OpDHs that exist as monomers...
- Ganas P, Brandsch R. Uptake of L-nicotine and of 6-hydroxy-L-nicotine by Arthrobacter nicotinovorans and by Escherichia coli is mediated by facilitated diffusion and not by passive diffusion or active transport. Microbiology. 2009;155:1866-77 pubmed publisher..In contrast to the situation at the blood-brain barrier, nicotine transport across the cell membrane by these bacteria was not by passive diffusion or active transport but by facilitated diffusion. ..
- Bacchi C, Yarlett N, Faciane E, Bi X, Rattendi D, Weiss L, et al. Metabolism of an alkyl polyamine analog by a polyamine oxidase from the microsporidian Encephalitozoon cuniculi. Antimicrob Agents Chemother. 2009;53:2599-604 pubmed publisher..cuniculi. The results in this study demonstrate competitive inhibition of oxidase activity by BW-1 and support further studies of this oxidase activity by the parasite and host. ..
- Weisell J, Hyvonen M, Häkkinen M, Grigorenko N, Pietilä M, Lampinen A, et al. Synthesis and biological characterization of novel charge-deficient spermine analogues. J Med Chem. 2010;53:5738-48 pubmed publisher..5a was acetylated to 5c and 5b, and the latter was further metabolized by acetylpolyamine oxidase to 3a, a drug used to treat Wilson's disease. Thus, 5a is a bioactive precursor of 3a with enhanced bioavailability. ..
- Mumtaz H, Gupta V, Singh P, Marwaha R, Khandelwal N. MR imaging findings of glutaric aciduria type II. Singapore Med J. 2010;51:e69-71 pubmed..He was clinically diagnosed with diabetic ketoacidosis. However, on MR imaging, brain evaluation and laboratory analysis, he was found to have glutaric aciduria type II. ..
- Fujieda N, Mori M, Ikeda T, Kano K. The silent form of quinohemoprotein amine dehydrogenase from Paracoccus denitrificans. Biosci Biotechnol Biochem. 2009;73:524-9 pubmed..The UV-vis spectral properties of the gamma subunit of hydroxylamine-treated QH-AmDH were identical to those of sQH-AmDH. The hydroxylamine-treated QH-AmDH was also reactivated by butylamine, as in the case of sQH-AmDH. ..
- Ma J, Carrell C, Mathews F, Davidson V. Site-directed mutagenesis of proline 52 to glycine in amicyanin converts a true electron transfer reaction into one that is conformationally gated. Biochemistry. 2006;45:8284-93 pubmed..This same reaction step now also gates the ET from N-quinol MADH, which is normally rate-limited by a proton transfer. ..
- Abu Tarboush N, Jensen L, Feng M, Tachikawa H, Wilmot C, Davidson V. Functional importance of tyrosine 294 and the catalytic selectivity for the bis-Fe(IV) state of MauG revealed by replacement of this axial heme ligand with histidine . Biochemistry. 2010;49:9783-91 pubmed publisher..Thus, a critical feature of the bis-Fe(IV) species may be that it shortens the electron transfer distance from preMADH to a high-valent heme iron. ..
- Kanika N, Tar M, Tong Y, Kuppam D, Melman A, Davies K. The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway. Am J Physiol Cell Physiol. 2009;297:C916-27 pubmed publisher..Our results suggest that the upregulation of enzymes involved in the polyamine synthetic pathway may play a role in the development of experimental priapism and represent a target for the prevention of priapism. ..
- Bjelakovic G, Beninati S, Bjelakovic B, Sokolovic D, Jevtovic T, Stojanovic I, et al. Does polyamine oxidase activity influence the oxidative metabolism of children who suffer of diabetes mellitus?. Mol Cell Biochem. 2010;341:79-85 pubmed publisher..The findings of higher blood HbA(1C) and MDA levels confirm the presence of oxidant stress in children with type 1 diabetes mellitus and demonstrate that PAO activity may participate in these circumstances. ..
- Hong S, Chaturvedi R, Piazuelo M, Coburn L, Williams C, Delgado A, et al. Increased expression and cellular localization of spermine oxidase in ulcerative colitis and relationship to disease activity. Inflamm Bowel Dis. 2010;16:1557-66 pubmed publisher..SMO expression is upregulated in UC tissues, deriving from increased levels in mononuclear inflammatory cells. Dysregulated polyamine homeostasis may contribute to chronic UC by altering immune responses and increasing oxidative stress. ..
- Kachalova G, Bourenkov G, Mengesdorf T, Schenk S, Maun H, Burghammer M, et al. Crystal structure analysis of free and substrate-bound 6-hydroxy-L-nicotine oxidase from Arthrobacter nicotinovorans. J Mol Biol. 2010;396:785-99 pubmed publisher..The two enzymes are proposed to orient the enantiomeric substrates in mirror symmetry with respect to the plane of the flavin. ..
- Chen H, Attieh Z, Syed B, Kuo Y, Stevens V, Fuqua B, et al. Identification of zyklopen, a new member of the vertebrate multicopper ferroxidase family, and characterization in rodents and human cells. J Nutr. 2010;140:1728-35 pubmed publisher..Knockdown with small interfering RNA in BeWo cells indicates that this gene represents the previously detected oxidase. We propose calling this new member of the MCF family "zyklopen." ..