当前位置： SCI文献检索 > BIOCHEMISTRY期刊下所有文献 > Local destabilization of the metal-binding region in human copper-zinc superoxide dismutase by remote mutations is a possible determinant for progression of ALS.

Local destabilization of the metal-binding region in human copper-zinc superoxide dismutase by remote mutations is a possible determinant for progression of ALS.

Abstract：

:More than 100 distinct mutations in the gene CuZnSOD encoding human copper-zinc superoxide dismutase (CuZnSOD) have been associated with familial amyotrophic lateral sclerosis (fALS), a fatal neuronal disease. Many studies of different mutant proteins have found effects on protein stability, catalytic activity, and metal binding, but without a common pattern. Notably, these studies were often performed under conditions far from physiological. Here, we have used experimental conditions of pH 7 and 37 °C and at an ionic strength of 0.2 M to mimic physiological conditions as close as possible in a sample of pure protein. Thus, by using NMR spectroscopy, we have analyzed amide hydrogen exchange of the fALS-associated I113T CuZnSOD variant in its fully metalated state, both at 25 and 37 °C, where (15)N relaxation data, as expected, reveals that CuZnSOD I113T exists as a dimer under these conditions. The local dynamics at 82% of all residues have been analyzed in detail. When compared to the wild-type protein, it was found that I113T CuZnSOD is particularly destabilized locally at the ion binding sites of loop 4, the zinc binding loop, which results in frequent exposure of the aggregation prone outer β-strands I and VI of the β-barrel, possibly enabling fibril or aggregate formation. A similar study (Museth, A. K., et al. (2009) Biochemistry, 48, 8817-8829) of amide hydrogen exchange at pH 7 and 25 °C on the G93A variant also revealed a selective destabilization of the zinc binding loop. Thus, a possible scenario in ALS is that elevated local dynamics at the metal binding region can result in toxic species from formation of new interactions at local β-strands.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Hennig J,Andrésen C,Museth AK,Lundström P,Tibell LA,Jonsson BH

doi

10.1021/bi500606j

subject

Has Abstract

pub_date

2015-01-20 00:00:00

pages

323-33

issue

2

eissn

0006-2960

issn

1520-4995

journal_volume

54

pub_type

杂志文章

相关文献

BIOCHEMISTRY文献大全
  • Characterization of a heparin-binding site on the catalytic domain of factor XIa: mechanism of heparin acceleration of factor XIa inhibition by the serpins antithrombin and C1-inhibitor.

    abstract：:Heparin accelerates inhibition of factor XIa (fXIa) by the serpins antithrombin (AT) and C1-inhibitor (C1-INH) by more than 2 orders of magnitude. The mechanism of the heparin-mediated acceleration of fXIa inhibition by these serpins is incompletely understood, as heparin appears to interact with both the catalytic an...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi802298r

    authors： Yang L,Sun MF,Gailani D,Rezaie AR

    更新日期：2009-02-24 00:00:00

  • Distance between the visible copper and cytochrome a in bovine heart cytochrome oxidase.

    abstract：:Electron paramagnetic resonance (EPR) at 15 K was used to probe the magnetic interaction between the visible copper CuA2+ and ferric cytochrome a in the carbon monoxide compound of beef heart cytochrome oxidase. At pH 8.6, the midpoint potentials (Em's) for one-electron oxidation of CuA+ and cytochrome a2+ were found ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00330a028

    authors： Goodman G,Leigh JS Jr

    更新日期：1985-04-23 00:00:00

  • Resonance Raman and electronic absorption spectral studies of some beta-(2-furyl)acryloylglyceraldehyde-3-phosphate dehydrogenases.

    abstract：:Electronic absorption and resonance Raman spectra, together with rates of arsenolysis, are used to show that the acylated subunits of the rabbit furylacryloylglyceraldehyde-3-phosphate dehydrogenase (FA-rabbit enzyme), but not the FA-sturgeon enzyme, exist as a mixed population of at least two forms. One form of the F...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00515a023

    authors： Storer AC,Phelps DJ,Carey PR

    更新日期：1981-06-09 00:00:00

  • Escherichia coli cAMP receptor protein-DNA complexes. 1. Energetic contributions of half-sites and flanking sequences in DNA recognition.

    abstract：:In Escherichia coli, the cyclic AMP receptor protein (CRP) serves as a sensor of the intracellular level of cyclic AMP. At increasing concentrations of cyclic AMP, CRP becomes activated upon binding a cyclic AMP molecule. The activated CRP is capable of regulating the expression of more than 20 genes by binding to spe...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi972450i

    authors： Pyles EA,Chin AJ,Lee JC

    更新日期：1998-04-14 00:00:00

  • 51V NMR study of vanadate binding to myosin and its subfragment 1.

    abstract：:The binding of various forms of vanadate to myosin and myosin subfragment 1 (S-1) was studied by 51V NMR at increasing vanadate concentrations between 0.06 and 1.0 mM. The distribution of the various forms of vanadate in the solution depended on the total concentration of vanadate. At low concentrations, the predomina...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00490a029

    authors： Ringel I,Peyser YM,Muhlrad A

    更新日期：1990-09-25 00:00:00

  • Processes of base-pair opening and proton exchange in Z-DNA.

    abstract：:Using proton magnetic resonance, we have investigated imino and amino proton exchange in the Z form of the four oligomers d(Cbr8GCGCbr8G), d(CGm5CGCG), d(CG)6, and d(CG)12. In the latter two oligomers, all five exchangeable protons have been assigned. We find that proton acceptors such as NH3 or the basic form of Tris...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00472a008

    authors： Kochoyan M,Leroy JL,Guéron M

    更新日期：1990-05-22 00:00:00

  • Fidelity of DNA synthesis by the Thermus aquaticus DNA polymerase.

    abstract：:We have determined the fidelity of in vitro DNA synthesis catalyzed at high temperature by the DNA polymerase from the thermophilic bacterium Thermus aquaticus. Using a DNA substrate that contains a 3'-OH terminal mismatch, we demonstrate that the purified polymerase lacks detectable exonucleolytic proofreading activi...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00416a027

    authors： Tindall KR,Kunkel TA

    更新日期：1988-08-09 00:00:00

  • Surface salt bridges, double-mutant cycles, and protein stability: an experimental and computational analysis of the interaction of the Asp 23 side chain with the N-terminus of the N-terminal domain of the ribosomal protein l9.

    abstract：:Experimental and theoretical double-mutant cycles have been used to investigate a salt bridge in the N-terminal domain of the protein L9. Aspartic acid 23 is the only acidic residue involved in a well-defined pairwise interaction, namely, a partially solvent-exposed salt bridge with the protonated N-terminus of the pr...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi027202n

    authors： Luisi DL,Snow CD,Lin JJ,Hendsch ZS,Tidor B,Raleigh DP

    更新日期：2003-06-17 00:00:00

  • Oxindolealanine-62 lysozyme: equilibrium, calorimetric, and kinetic studies of the reaction with N-acetylglucosamine oligosaccharides.

    abstract：:Oxindolealanine-62 lysozyme, formed by reaction with N-bromosuccinimide and purified by using affinity chromatography, was examined in its binding of homologous oligosaccharides of N-acetylglucosamine and in its catalysis of hydrolysis and of transglycosylation of the hexasaccharide of N-acetylglucosamine. Equilibrium...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00558a022

    authors： Shrake A,Rupley JA

    更新日期：1980-08-19 00:00:00

  • A host-guest relationship in bone morphogenetic protein receptor-II defines specificity in ligand-receptor recognition.

    abstract：:One of the most intriguing questions confronting the bone morphogenetic protein family is the mechanism of ligand recognition, because there are more ligands than receptors. Crystal structures of two type II receptors, ActR-II and BMPR-II, are essentially identical, and a loop structure (A-loop) has been suggested to ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi3003023

    authors： Yeh LC,Falcon WE,Garces A,Lee JC,Lee JC

    更新日期：2012-09-04 00:00:00

  • Bacillus megaterium CYP102A1 oxidation of acyl homoserine lactones and acyl homoserines.

    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

    authors： Chowdhary PK,Keshavan N,Nguyen HQ,Peterson JA,González JE,Haines DC

    更新日期：2007-12-18 00:00:00

  • The 2.15 A crystal structure of Mycobacterium tuberculosis chorismate mutase reveals an unexpected gene duplication and suggests a role in host-pathogen interactions.

    abstract：:Chorismate mutase catalyzes the first committed step toward the biosynthesis of the aromatic amino acids, phenylalanine and tyrosine. While this biosynthetic pathway exists exclusively in the cell cytoplasm, the Mycobacterium tuberculosis enzyme has been shown to be secreted into the extracellular medium. The secretor...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi0606445

    authors： Qamra R,Prakash P,Aruna B,Hasnain SE,Mande SC

    更新日期：2006-06-13 00:00:00

  • Interactions of diastereomeric tripeptides of lysyl-5-fluorotryptophyllysine with DNA. 1. Optical and 19F NMR studies of native DNA complexes.

    abstract：:Lysyl-5-fluoro-L-tryptophyllysine and lysyl-5-fluoro-D-tryptophyllysine were synthesized, and their interactions with double-stranded DNA were investigated as a model for protein-nucleic acid interactions. The binding to DNA was studied by monitoring various 19F NMR parameters, the fluorescence, and the optical absorb...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00337a012

    authors： Shine NR,James TL

    更新日期：1985-07-30 00:00:00

  • The N-terminal fragment of human parathyroid hormone receptor 1 constitutes a hormone binding domain and reveals a distinct disulfide pattern.

    abstract：:The N-terminal extracellular parts of human G-protein coupled receptor class B, for example, receptors for secretin, glucagon, or parathyroid hormone, are involved in ligand binding. To obtain structural and functional information on the N-terminal receptor fragment of human parathyroid hormone receptor 1 (PTHR1), the...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi0001426

    authors： Grauschopf U,Lilie H,Honold K,Wozny M,Reusch D,Esswein A,Schäfer W,Rücknagel KP,Rudolph R

    更新日期：2000-08-01 00:00:00

  • How does a DNA interacting enzyme change its specificity during molecular evolution? A site-directed mutagenesis study at the DNA binding site of the DNA-(adenine-N6)-methyltransferase EcoRV.

    abstract：:The EcoRV DNA-(adenine-N6)-methyltransferase (MTase) recognizes GATATC sequences and modifies the first adenine residue within this site. Parts of its DNA interface show high sequence homology to DNA MTases of the dam family which recognize and modify GATC sequences. A phylogenetic analysis of M.EcoRV and dam-MTases s...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi0155450

    authors： Beck C,Cranz S,Solmaz M,Roth M,Jeltsch A

    更新日期：2001-09-18 00:00:00

  • (+/-)-(1S,2R,5S)-5-Amino-2-fluorocyclohex-3-enecarboxylic acid. A potent GABA aminotransferase inactivator that irreversibly inhibits via an elimination-aromatization pathway.

    abstract：:Inhibition of gamma-aminobutyric acid aminotransferase (GABA-AT) increases the concentration of GABA, an inhibitory neurotransmitter in human brain, which could have therapeutic applications for a variety of neurological diseases, including epilepsy. On the basis of studies of several previously synthesized conformati...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi061592m

    authors： Wang Z,Yuan H,Nikolic D,Van Breemen RB,Silverman RB

    更新日期：2006-12-05 00:00:00

  • Peptidyl aldehydes as reversible covalent inhibitors of SRC homology 2 domains.

    abstract：:Src homology 2 (SH2) domains are phosphotyrosine- (pY-) binding modules found in a variety of signal-transducing proteins and constitute an important class of drug targets for the treatment of signaling related diseases/conditions. To date, a large number of peptidic as well as nonpeptidic SH2 domain inhibitors have b...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi034076u

    authors： Park J,Fu H,Pei D

    更新日期：2003-05-06 00:00:00

  • Characterization of a genomic and cDNA clone coding for the thioesterase domain and 3' noncoding region of the chicken liver fatty acid synthase gene.

    abstract：:The fatty acid synthase (FAS) of animal tissue is a dimer of two identical subunits, each with a Mr of 260,000. The subunit is a single multifunctional protein having seven catalytic activities and a site for binding of the prosthetic group 4'-phosphopantetheine. The mRNA coding for the subunit has an estimated size o...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00420a029

    authors： Kasturi R,Chirala S,Pazirandeh M,Wakil SJ

    更新日期：1988-10-04 00:00:00

  • Rates of oxygen and hydrogen exchange as indicators of TPQ cofactor orientation in amine oxidases.

    abstract：:This study presents the first detailed examination by resonance Raman (RR) spectroscopy of the rates of solvent exchange for the C5 and C3 positions of the TPQ cofactor in several wild-type copper-containing amine oxidases and mutants of the amine oxidase from Hansenula polymorpha (HPAO). On the basis of crystal struc...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi011685y

    authors： Green EL,Nakamura N,Dooley DM,Klinman JP,Sanders-Loehr J

    更新日期：2002-01-15 00:00:00

  • Dipeptide metalloendoprotease substrates are glucose transport inhibitors and membrane structure perturbants.

    abstract：:Dipeptide substrates for metalloendoproteases have previously been shown to block biological processes requiring membrane fusion. Thus, we employed such compounds as potential inhibitors of the insulin-dependent activation of glucose transport in fat cells. This event is thought to involve vesicle movement from an int...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00361a031

    authors： Aiello LP,Wessling-Resnick M,Pilch PF

    更新日期：1986-07-01 00:00:00

  • Phosphorylation of beta III-tubulin.

    abstract：:There is considerable evidence that mammalian beta-tubulin is phosphorylated. Specifically, of the seven beta isotypes, the phosphorylated one is beta III, the isotype found almost entirely in neurons. The phosphate is added at a serine and perhaps a tyrosine near the C-terminus. All the evidence to date has been gath...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi951247p

    authors： Khan IA,Ludueña RF

    更新日期：1996-03-26 00:00:00

  • Structure of pseudobactin A214, a siderophore from a bean-deleterious Pseudomonas.

    abstract：:Bean-deleterious Pseudomonas A214 produced the extracellular yellow-green, fluorescent siderophore [microbial iron(III) transport agent] pseudobactin A214 under iron-limiting conditions. Pseudobactin A214 has a molecular formula of C46H64N13O22 and a molecular mass of 1151 g/mol. Pseudobactin A214 contained an N-block...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00367a022

    authors： Buyer JS,Wright JM,Leong J

    更新日期：1986-09-23 00:00:00

  • Hydrogen bonding networks tune proton-coupled redox steps during the enzymatic six-electron conversion of nitrite to ammonia.

    abstract：:Multielectron multiproton reactions play an important role in both biological systems and chemical reactions involved in energy storage and manipulation. A key strategy employed by nature in achieving such complex chemistry is the use of proton-coupled redox steps. Cytochrome c nitrite reductase (ccNiR) catalyzes the ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi500854p

    authors： Judd ET,Stein N,Pacheco AA,Elliott SJ

    更新日期：2014-09-09 00:00:00

  • Subunit disassembly and unfolding kinetics of hemoglobin studied by time-resolved electrospray mass spectrometry.

    abstract：:We report the use of electrospray ionization (ESI) mass spectrometry (MS) in conjunction with online rapid mixing to monitor the kinetics of acid-induced ferrihemoglobin denaturation. Under equilibrium conditions, the hemoglobin mass spectrum is dominated by the intact heterotetramer. Dimeric and monomeric species are...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi048501a

    authors： Simmons DA,Wilson DJ,Lajoie GA,Doherty-Kirby A,Konermann L

    更新日期：2004-11-23 00:00:00

  • Specific stimulation of the T7 gene 6 exonuclease by the phage T7 coded deoxyribonucleic acid binding protein.

    abstract：:Bacteriophage T7 codes for a single-stranded DNA binding protein. This protein is the product of gene 2.5 and has been found previously to stimulate specifically the activity of the phage-coded DNA polymerase. We report here that the T7 DNA binding protein also stimulates the activity of the phage-coded exonuclease. T...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00266a042

    authors： Roberts L,Sadowski P,Wong JT

    更新日期：1982-11-09 00:00:00

  • Reactivity of penicillin-binding proteins with peptidoglycan-mimetic beta-lactams: what's wrong with these enzymes?

    abstract：:Beta-lactams exert their antibiotic action through their inhibition of bacterial DD-peptidases (penicillin-binding proteins). Bacteria, in general, carry several such enzymes localized on the outside of their cell membrane to catalyze the final step in cell wall (peptidoglycan) synthesis. They have been classified int...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi061804f

    authors： Josephine HR,Charlier P,Davies C,Nicholas RA,Pratt RF

    更新日期：2006-12-26 00:00:00

  • Comparative electron paramagnetic resonance study of radical intermediates in turnip peroxidase isozymes.

    abstract：:The occurrence of isozymes in plant peroxidases is poorly understood. Turnip roots contain seven season-dependent isoperoxidases with distinct physicochemical properties. In the work presented here, multifrequency electron paramagnetic resonance spectroscopy has been used to characterize the Compound I intermediate ob...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi002826j

    authors： Ivancich A,Mazza G,Desbois A

    更新日期：2001-06-12 00:00:00

  • Stoichiometry and specificity of lipid-protein interaction with myelin proteolipid protein studied by spin-label electron spin resonance.

    abstract：:The interaction of spin-labeled lipids with the myelin proteolipid apoprotein in complexes with dimyristoylphosphatidylcholine of varying lipid/protein ratios has been studied with electron spin resonance spectroscopy. A first shell of approximately 10 lipids per 25 000-dalton protein is found to be motionally restric...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00300a011

    authors： Brophy PJ,Horváth LI,Marsh D

    更新日期：1984-02-28 00:00:00

  • Regulation of the expression of the β-lactam antibiotic-resistance determinants in methicillin-resistant Staphylococcus aureus (MRSA).

    abstract：:β-Lactam antibiotics have faced obsolescence with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). A complex set of events ensues upon exposure of MRSA to these antibiotics, which culminates in proteolysis of BlaI or MecI, two gene repressors, and results in the induction of resistance. We report s...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi500074w

    authors： Blázquez B,Llarrull LI,Luque-Ortega JR,Alfonso C,Boggess B,Mobashery S

    更新日期：2014-03-18 00:00:00

  • Transthyretin aggregation under partially denaturing conditions is a downhill polymerization.

    abstract：:The deposition of fibrils and amorphous aggregates of transthyretin (TTR) in patient tissues is a hallmark of TTR amyloid disease, but the molecular details of amyloidogenesis are poorly understood. Tetramer dissociation is typically rate-limiting for TTR amyloid fibril formation, so we have used a monomeric variant o...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi049621l

    authors： Hurshman AR,White JT,Powers ET,Kelly JW

    更新日期：2004-06-15 00:00:00