Abstract：
:Conformational changes in the prion protein cause transmissible spongiform encephalopathies, also referred to as prion diseases. In its native state, the prion protein is innocuous (PrPC), but it can misfold into a neurotoxic and infectious isoform (PrPSc). The full-length cellular form of the prion protein consists of residues 23-230, with over half of the sequence belonging to the unstructured N-terminal domain and the remaining residues forming a small globular domain. During misfolding and aggregation, portions of both the structured and unstructured domains are incorporated into the aggregates. After limited proteolysis by proteinase K, the most abundant fragment from brain-derived prion fibrils is a 141-residue fragment composed of residues 90-230. Here we describe simulations of this fragment of the human prion protein at low pH, which triggers misfolding, and at neutral pH as a control. The simulations, in agreement with experiment, show that this biologically and pathologically relevant prion construct is stable and native-like at neutral pH. In contrast, at low pH the prion protein is destabilized via disruption of critical long-range salt bridges. In one of the low pH simulations this destabilization resulted in a conformational transition to a PrPSc-like isoform consistent with our previous simulations of a smaller construct.
journal_name
Biochemistryjournal_title
Biochemistryauthors
DeMarco ML,Daggett Vdoi
10.1021/bi0619066subject
Has Abstractpub_date
2007-03-20 00:00:00pages
3045-54issue
11eissn
0006-2960issn
1520-4995journal_volume
46pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:We have studied the tridecadeoxynucleotide CGCGAATTACGCG (I), which contains an additional A at position 9 compared to the dodecanucleotide of which the crystal structure has been determined. Sequence I exhibits no distinct melting curve and also has a concentration-dependent pattern of peaks on reverse-phase chromato...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00371a025
更新日期：1986-11-18 00:00:00
abstract：:Significant concentrations (1-10 mM) of nickel(II) were found in solution after incubation of the potent carcinogen nickel subsulfide in 0.05 M Tris-HCl, pH 7.4, solutions containing DNA, rat liver microsomes, and NADPH. The presence of NADPH decreased the rate of solubilization of nickel subsulfide. The solubilized n...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00533a030
更新日期：1982-02-16 00:00:00
abstract：:The constant (CL) fragment of the immunoglobulin light chain contains only one intrachain disulfide bond buried in the interior of the molecule. The kinetics of reduction with dithiothreitol of the disulfide bond were studied at various concentrations of guanidine hydrochloride at pH 8.0 and 25 degrees C. It was found...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00356a026
更新日期：1986-04-22 00:00:00
abstract：:Previous studies of Escherichia coli dihydrofolate reductase (ecDHFR) have demonstrated that residue G121, which is 19 A from the catalytic center, is involved in catalysis, and long distance dynamical motions were implied. Specifically, the ecDHFR mutant G121V has been extensively studied by various experimental and ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0518242
更新日期：2006-02-07 00:00:00
abstract：:Oligodeoxyribonucleotides 8-12 nucleotides in length whose sequences are complementary to the 5' end, the initiation codon regions, or the coding regions of rabbit globin mRNA were tested for their ability to inhibit translation in a rabbit reticulocyte lysate and in a wheat germ extract. The oligomers interact specif...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00343a015
更新日期：1985-10-22 00:00:00
abstract：:The presence of a N-(2-deoxy-D-erythro pentofuranosyl)urea (henceforth referred to as deoxyribosylurea) residue, ring fragmentation product of a thymine, in a frameshift situation in the sequence 5'd(AGGACCACG).d(CGTGGurTCCT) has been studied by 1H and 31P nuclear magnetic resonance and molecular dynamics. At equilibr...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi971202j
更新日期：1998-01-27 00:00:00
abstract：:Periodate-oxidized tRNA(Phe) (tRNA(oxPhe)) behaves as a specific affinity label of tetrameric Escherichia coli phenylalanyl-tRNA synthetase (PheRS). Reaction of the alpha 2 beta 2 enzyme with tRNA(oxPhe) results in the loss of tRNAPhe aminoacylation activity with covalent attachment of 2 mol of tRNA dialdehyde/mol of ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00391a033
更新日期：1987-08-25 00:00:00
abstract：:Photolyases reverse the effects of UV light on cells by converting cyclobutane dipyrimidine photoproducts (pyrimidine dimers, Pyr mean value of Pyr) into pyrimidine monomers in a light-dependent reaction. Previous work has suggested that, based on substrate preference, there are two classes of photolyase: DNA photolya...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00099a019
更新日期：1991-09-03 00:00:00
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
更新日期：2014-03-18 00:00:00
abstract：:The solution structure of the C-terminal fragment 255-316 of thermolysin has been determined by two-dimensional proton NMR methods. For this disulfide-free fragment there was a previous proposal according to which it would fold into a stable helical structure forming a dimer at concentrations above 0.06 mM. A complete...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00253a023
更新日期：1994-12-13 00:00:00
abstract：:The equilibrium binding of hemoglobin to isolated band 3 protein exhibited positive cooperativity [Hill coefficient = 1.65 +/- 0.1; total number of binding sites at pH 6.6 in 5 mM sodium phosphate buffer = 32 500 +/- 940 pmol/mg; Ka = (3.0 +/- 0.5) X 10(5) M-1]. The binding was reversible and ionic in nature as the bo...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00359a054
更新日期：1986-06-03 00:00:00
abstract：:The reversible inhibition of beta-lactamase I from Bacillus cereus by cloxacillin, methicillin, and nafcillin has been systematically investigated. For these substrates the enzymatic reaction involves partitioning of the substrate between turnover and inhibition. Typically, concentrations of several hundred millimolar...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00388a011
更新日期：1987-07-14 00:00:00
abstract：:Primase is an essential DNA replication enzyme in Escherichia coli and responsible for primer synthesis during lagging strand DNA replication. Although the interaction of primase with single-stranded DNA plays an important role in primer RNA and Okazaki fragment synthesis, the mechanism of DNA binding and site selecti...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi026711m
更新日期：2002-12-17 00:00:00
abstract：:The site-directed mutagenesis of a number of proposed active site residues of 5-enolpyruvyl shikimate-3-phosphate (EPSP) synthase is reported. Several of these mutations resulted in complete loss of enzyme activity indicating that these residues are probably involved with catalysis, notably K22R, K411R, D384A, R27A, R...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9815142
更新日期：1999-01-05 00:00:00
abstract：:Biochemical analysis of a rat fibroblast cell clone, transfected with the murine Ia associated invariant chain gene, demonstrates the expression of a family of proteins. This indicates that all members of the invariant protein family are derived from the same gene. The proteins p41, Ii, p27, p25, and p10, synthesized ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00411a028
更新日期：1988-05-31 00:00:00
abstract：:Investigation of the charge distribution for all known members of the PP-fold family of peptides reveals a common pattern characterized by a cluster of negative charges in the beta-turn region and a cluster of positive charges in the receptor-binding region of the peptide. Detailed analysis of the electrostatic proper...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00063a005
更新日期：1993-03-30 00:00:00
abstract：:Four-coordinate metalloporphyrins activate soluble guanylyl cyclase. Ni(II)PPIX and Cu(II)PPIX are high affinity activators, with activation constants of 24 and 17 nM, respectively. Both metalloporphyrins remain stably bound to the enzyme, enabling spectroscopic characterization of the Ni(II)- and Cu(II)-reconstituted...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi010777k
更新日期：2002-08-06 00:00:00
abstract：:The effects of pH on the kinetics of association and dissociation of chymotrypsin and the dipeptidyl trifluoromethyl ketone (TFK) N-acetyl-L-leucyl-L-phenylalanyltrifluoromethane (1) were examined through the pH range 4-9.5. The pH dependence of the association rate (kon) is similar to that of kcat/Km for ester and pe...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00449a017
更新日期：1989-11-14 00:00:00
abstract：:The thermal denaturation of the cupredoxin plastocyanin (PC) from spinach has been studied with the aim of improving the understanding of factors involved in the conformational stability of antiparallel beta-sheet proteins. Studies using differential scanning calorimetry have been complemented with nuclear magnetic re...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi034371e
更新日期：2003-09-02 00:00:00
abstract：:The potassium form of d(CGCGAATTCGCG) solved by X-ray diffraction to 1.75 A resolution indicates that monovalent cations penetrate the primary and secondary layers of the "spine of hydration". Both the sodium [Shui, X., McFail-Isom, L., Hu, G. G., and Williams, L. D. (1998) Biochemistry 37, 8341-8355] and the potassiu...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi982063o
更新日期：1998-12-01 00:00:00
abstract：:Sufiredoxins (Srx) repair the inactivated forms of typical two-Cys peroxiredoxins (Prx) implicated in hydrogen peroxide-mediated cell signaling. The reduction of the cysteine sulfinic acid moiety within the active site of the Prx by Srx involves novel sulfur chemistry and the use of ATP and Mg(2+). The 1.65 A crystal ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi050131i
更新日期：2005-06-21 00:00:00
abstract：:Antifreeze proteins (AFPs) inhibit the growth of ice by binding to the surface of ice crystals, preventing the addition of water molecules to cause a local depression of the freezing point. AFPs from insects are much more effective at depressing the freezing point than fish AFPs. Here, we have investigated the possibi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi035605x
更新日期：2004-01-13 00:00:00
abstract：:S-(4-Bromo-2,3-dioxobutyl)glutathione (S-BDB-G), a reactive analogue of glutathione, has been synthesized and characterized by UV spectroscopy and thin-layer chromatography, as well as by bromide and primary amine analysis. Incubation of S-BDB-G (200 microM) with the 4-4 isoenzyme of rat liver glutathione S-transferas...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00111a006
更新日期：1991-11-26 00:00:00
abstract：:Lactone-hydrolyzing enzymes derived from some Bacillus species are capable of disrupting quorum sensing in bacteria that use N-acyl-l-homoserine lactones (AHLs) as intercellular signaling molecules. Despite the promise of these quorum-quenching enzymes as therapeutic and anti-biofouling agents, the ring opening mechan...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi061238o
更新日期：2006-11-07 00:00:00
abstract：:Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone involved in the maintenance of the corpus luteum in early pregnancy. The free alpha-subunit of hCG has a biological activity of its own, namely, stimulation of prolactin secretion from term pregnancy decidual cells [Blithe, D. L., et al. (1991)...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9718548
更新日期：1998-02-17 00:00:00
abstract：:The mechanism of activation of cGMP phosphodiesterase by the GTP-binding protein in the disc membrane of retinal rods has been investigated by measuring the light-induced phosphodiesterase activity in reconstituted systems where the concentration of either the GTP-binding protein or the phosphodiesterase is varied. Th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00444a040
更新日期：1989-09-05 00:00:00
abstract：:The behavior of fluorescent and spin-label probes is examined in several fluid and gel phospholipid phases, with particular focus on the Ca2+-induced gel phase in phosphatidylserine (PS). These probes have behavior characteristic of the type of probe and of the type of lipid environment. Anthroyloxy- and doxyl-labeled...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00380a039
更新日期：1987-03-24 00:00:00
abstract：:Mistic is an unusual membrane protein from Bacillus subtilis. It appears to fold and insert autonomously into a lipid bilayer and has been suggested as a tool that aids the targeting of eukaryotic membrane proteins to bacterial membranes. The NMR structure of Mistic in detergent (LDAO) micelles has revealed it to be a...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0608818
更新日期：2006-08-01 00:00:00
abstract：:In Bacillus subtilis, P protein is the noncatalytic component of ribonuclease P (RNase P) that is critical for achieving maximal nuclease activity under physiological conditions. P protein is predominantly unfolded (D) at neutral pH and low ionic strength; however, it folds upon the addition of sulfate anions (ligands...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0504613
更新日期：2005-10-04 00:00:00
abstract：:CDP-ribitol synthase is a bifunctional reductase and cytidylyltransferase that catalyzes the transformation of D-ribulose 5-phosphate, NADPH, and CTP to CDP-ribitol, a repeating unit present in the virulence-associated polysaccharide capsules of Haemophilus influenzae types a and b [Follens, A., et al. (1999) J. Bacte...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi002745n
更新日期：2001-04-24 00:00:00
