Abstract：
:Despite a lack of convincing in vitro evidence and a number of sound refutations, it is widely accepted that renalase is an enzyme unique to animals that catalyzes the oxidative degradation of catecholamines in blood in order to lower vascular tone. Very recently, we identified isomers of β-NAD(P)H as substrates for renalase (Beaupre, B. A. et al. (2015) Biochemistry, 54, 795-806). These molecules carry the hydride equivalent on the 2 or 6 position of the nicotinamide base and presumably arise in nonspecific redox reactions of nicotinamide dinucleotides. Renalase serves to rapidly oxidize these isomers to form β-NAD(P)⁺ and then pass the electrons to dioxygen, forming H₂O₂. We have also shown that these substrate molecules are highly inhibitory to dehydrogenase enzymes and thus have proposed an intracellular metabolic role for this enzyme. Here, we identify a renalase from an organism without a circulatory system. This bacterial form of renalase has the same substrate specificity profile as that of human renalase but, in terms of binding constant (K(d)), shows a marked preference for substrates derived from β-NAD⁺. 2-dihydroNAD(P) substrates reduce the enzyme with rate constants (k(red)) that greatly exceed those for 6-dihydroNAD(P) substrates. Taken together, k(red)/K(d) values indicate a minimum 20-fold preference for 2DHNAD. We also offer the first structures of a renalase in complex with catalytically relevant ligands β-NAD⁺ and β-NADH (the latter being an analogue of the substrate(s)). These structures show potential electrostatic repulsion interactions with the product and a unique binding orientation for the substrate nicotinamide base that is consistent with the identified activity.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Hoag MR,Roman J,Beaupre BA,Silvaggi NR,Moran GRdoi
10.1021/acs.biochem.5b00451subject
Has Abstractpub_date
2015-06-23 00:00:00pages
3791-802issue
24eissn
0006-2960issn
1520-4995journal_volume
54pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:Histidinol-phosphate aminotransferase (HspAT) is a key enzyme on the histidine biosynthetic pathway. HspAT catalyzes the transfer of the amino group of L-histidinol phosphate (Hsp) to 2-oxoglutarate to form imidazole acetol phosphate (IAP) and glutamate. Thus, HspAT recognizes two kinds of substrates, Hsp and glutamat...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi002769u
更新日期：2001-04-17 00:00:00
abstract：:Sulfonylureas and glinides are commonly used oral insulin secretagogues (ISs) that act on the pancreatic ATP-sensitive potassium (KATP) channel to promote insulin secretion in order to lower the blood glucose level. Physiologically, KATP channels are inhibited by intracellular ATP and activated by Mg-ADP. Therefore, t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.9b00692
更新日期：2020-01-14 00:00:00
abstract：:DNA-binding geometry and dynamics of a number of anthracyclines, including adriamycin and 4-demethoxydaunorubicin, interacting with DNA have been studied by means of linear dichroism and fluorescence techniques. The anthracycline chromophore is found to be approximately parallel to the plane of the DNA bases and to ha...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00421a024
更新日期：1988-10-18 00:00:00
abstract：:Glycophorin A is a sialoglycoprotein isolated from human erythrocyte membranes which seems to exist as stable dimeric complexes in the presence of sodium dodecyl sulfate. When analyzed by dodecyl sulfate acrylamide electrophoresis this molecule forms two PAS-stainable bands (PAS-U and PAS-2) which are reversibly inter...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00650a028
更新日期：1976-03-09 00:00:00
abstract：:Doublet signal and singlet-like signal induced in Ca(2+)-depleted PS II were investigated by pulsed EPR in one-dimensionally oriented photosystem (PS) II membranes. The doublet signal showed marked angular dependent change in its spectrum in term of the applied magnetic field, indicating that the magnetic dipole-dipol...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9929406
更新日期：2000-09-12 00:00:00
abstract：:The association state of the mannitol-specific enzyme II (EIIMtl) has been studied both in the purified form and embedded in the cytoplasmic membrane. Membrane fragments obtained from mannitol-grown Escherichia coli catalyze the phosphoenolpyruvate- (PEP) dependent phosphorylation of both glucose and mannitol; thus th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00319a003
更新日期：1984-11-20 00:00:00
abstract：:The sequential solid-phase synthesis of a peptide analogue of bovine brain calmodulin calcium binding site III covering residues 81-113 of the natural sequence is described. Methionine-109 is replaced by a leucine residue to avoid complications in the synthesis and purification. In an attempt to relate the structure o...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00393a019
更新日期：1987-09-22 00:00:00
abstract：:Human S100A7 (psoriasin) is a metal-chelating protein expressed by epithelial cells. It is a 22-kDa homodimer with two EF-hand domains per subunit and two transition-metal-binding His3Asp sites at the dimer interface. Each subunit contains two cysteine residues that can exist as free thiols (S100A7red) or as an intram...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.7b00781
更新日期：2017-10-31 00:00:00
abstract：:The aminoglycoside 6'-N-acetyltransferase AAC(6')-Ii from Enterococcus faecium is an important microbial resistance determinant and a member of the GCN5-related N-acetyltransferase (GNAT) superfamily. We report here the further characterization of this enzyme in terms of the kinetic mechanism of acetyl transfer and id...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi034148h
更新日期：2003-06-03 00:00:00
abstract：:Phospholipase Cβ (PLCβ) enzymes hydrolyze phosphatidylinositol 4,5-bisphosphate to produce second messengers that regulate intracellular Ca2+, cell proliferation, and survival. Their activity is dependent upon interfacial activation that occurs upon localization to cell membranes. However, the molecular basis for how ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.7b00547
更新日期：2017-10-17 00:00:00
abstract：:The product of transesterification of phospholipid acyl chains and unesterified cholesterol (UC) by the enzyme lecithin:cholesterol acyltransferase (LCAT) is cholesteryl ester (CE). Activation of LCAT by apolipoprotein (apo) A-I on nascent (discoidal) high-density lipoproteins (HDL) is essential for formation of matur...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi901242k
更新日期：2009-12-01 00:00:00
abstract：:The number of free cysteines in each polypeptide of acetylcholine receptor from the electric organ of Torpedo californica has been assessed by alkylating the native protein with N-ethylmaleimide and iodoacetamide during homogenization of the tissue and alkylating the polypeptides with N-ethylmaleimide as they were unf...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00434a048
更新日期：1989-04-18 00:00:00
abstract：:Oocytes released en masse from pig ovaries were isolated in large quantities by using sieving techniques. The isolated oocytes were gently homogenized, and the largely intact zona pellucida "ghosts" were purified by using sieving techniques. Sufficient amounts of zonae were recovered to permit, for the first time, ade...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00543a017
更新日期：1980-01-22 00:00:00
abstract：:A rapid assay procedure was developed for cleavage of the N-terminal propeptides of procollagen. With the assay a neutral procollagen N-protease was purified about 300-fold from chick embryo tendon extract. The enzyme had an apparent molecular weight of 260 000 and a pH optimum of 7.4. Ca2+ was required for enzymic ac...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00608a002
更新日期：1978-07-25 00:00:00
abstract：:The lateral stalk of ribosomes constitutes the GTPase-associated center and is responsible for recruiting translation factors to the ribosomes. The eukaryotic stalk contains a P-complex, in which one molecule of uL10 (formerly known as P0) protein binds two copies of P1/P2 heterodimers. Unlike bacterial uL10, eukaryot...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.9b00528
更新日期：2019-09-10 00:00:00
abstract：:The inhibitory effects of guanosine 5'-(gamma-fluorotriphosphate) [GTP(gamma F)] on both the polymerization and the colchicine-dependent GTPase activity of calf brain tubulin have been studied. The results demonstrate that this analogue of GTP, with a fluorine atom on the gamma-phosphate, is a reversible competitive d...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00393a022
更新日期：1987-09-22 00:00:00
abstract：:The aromatic hydroxylation of six pairs of selectively deuterated monosubstituted benzenes was investigated with rat liver microsomes of various induction states. The substrates studied included 3,5-D2C6H3X (1a-6a) and 2,4,6-D3C6H2X (1b-6b), where X = Br, CN, NO2, OCH3, CH3, or Ph, respectively. The deuterium content ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00308a031
更新日期：1984-06-19 00:00:00
abstract：:Human lecithin:cholesterol acyltransferase (LCAT, E.C.2.3.1.43) is a serine-type esterase that contains six cysteines, two of which, Cys31 and Cys184, are free. The remaining cysteines form disulfide links. One of these is between Cys50 and Cys74 and the other is between Cys313 and Cys356. The cDNA of LCAT and mutants...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00063a021
更新日期：1993-03-30 00:00:00
abstract：:Steric constraints in the retinal binding pocket of sensory rhodopsin I (SR-I) are analyzed by studying effects of sample temperature and retinal analogs. The flash-induced yield of the earliest detected intermediate S610, which corresponds to the K intermediate in the bacteriorhodopsin (BR) photocycle, decreases belo...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00089a044
更新日期：1993-09-28 00:00:00
abstract：:Computer graphics and energy minimization techniques were used to construct a model of DNA containing cis-thymine glycol, an oxidation product of thymine formed in DNA by ionizing radiation. The model simulated an experimental DNA substrate used to study the effects of this lesion on DNA synthesis in vitro. The result...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00391a028
更新日期：1987-08-25 00:00:00
abstract：:Quorum sensing, the ability of bacteria to sense their own population density through the synthesis and detection of small molecule signals, has received a great deal of attention in recent years. Acyl homoserine lactones (AHLs) are a major class of quorum sensing signaling molecules. In nature, some bacteria that do ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi701945j
更新日期：2007-12-18 00:00:00
abstract：:Nitroxyl (HNO), a potential heart failure therapeutic, is known to target cysteine residues to form sulfinamides and/or disulfides. Because HNO-derived modifications may depend on their local environment, we have investigated the reactivity of HNO with cysteine derivatives and C-terminal cysteine-containing peptides a...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi500360x
更新日期：2014-06-10 00:00:00
abstract：:The heme and cysteine microenvironments of bluefin tuna apomyoglobin have been investigated by examining the fluorescence properties of two extrinsic chromophores, i.e., ANS and 1,5-AEDANS. 1,5-AEDANS was covalently bound to the single cysteine residue found in the primary structure of tuna apomyoglobin. Recombination...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00531a002
更新日期：1982-01-19 00:00:00
abstract：:Vitamin D receptor (VDR) is a member of the nuclear hormone receptor superfamily. When bound to a variety of vitamin D analogues, VDR manifests a wide diversity of physiological actions. The molecular mechanism by which different vitamin D analogues cause specific responses is not understood. The published crystallogr...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi201637p
更新日期：2011-12-27 00:00:00
abstract：:Amyloid beta peptide (A beta) is released into the media of a variety of cells in culture during normal metabolism. The discovery of several missense mutations within or flanking the A beta region of the beta amyloid precursor protein (beta APP) in familial Alzheimer's disease provides strong evidence for a role of al...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00181a016
更新日期：1994-04-19 00:00:00
abstract：:Evidence of nonequilibrium local heating in transient spectra of LHCII, the main light-harvesting complex of plants, was studied by using various excitation intensities over a wide temperature range, from 10 K to room temperature. No obvious manifestation of local heating was found at room temperature, whereas at 10 K...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi060048a
更新日期：2006-08-08 00:00:00
abstract：:The solution conformation of an agalactosyl penta-antennary "bisected" N-linked glycan from hen ovomucoid has been determined using a combination of 1H-NMR NOE measurements and restrained molecular dynamics (MD) simulations. The majority of glycosidic linkages exhibited restricted torsional fluctuations about the glob...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00043a018
更新日期：1995-10-31 00:00:00
abstract：:The interaction of poly(N epsilon, N epsilon, N epsilon-trimethyl-L-lysine) ([Lys(Me3)]n) and poly(N delta, N delta, N delta-trimethyl-L-ornithine) ([Orn(Me3)]n) with polynucleotides was studied by thermal denaturation, viscosity, and dissociation by salt. The methylated polymers decrease the viscosity of DNA in propo...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00555a020
更新日期：1980-07-08 00:00:00
abstract：:In Campylobacter jejuni 2,4-diacetamido-2,4,6-trideoxy-alpha-d-glucopyranose, termed N,N'-diacetylbacillosamine (Bac2,4diNAc), is the first carbohydrate in the glycoprotein N-linked heptasaccharide. With uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) as a starting point, two enzymes of the general protein glycos...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi061456h
更新日期：2006-11-14 00:00:00
abstract：:Transient contacts between denatured polypeptide chains are likely to play an important part in the initial stages of protein aggregation and fibrillation. To analyze the nature of such contacts, we have carried out a protein engineering study of the 102-residue protein U1A, which aggregates transiently in the wild-ty...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi048509k
更新日期：2004-10-19 00:00:00
