Abstract:
:Prion diseases are associated with the conversion of the normal prion protein, PrP(C), to the infectious disease form PrP(Sc). Discrimination between these isoforms would significantly enhance diagnosis of these diseases, and it has recently been reported that PrP(Sc) is specifically recognized by the serine protease zymogen plasminogen (Fischer et al. (2000) Nature 408, 479). Here we have tested the hypothesis that PrP is a regulator of the plasminogen activation system. The effect of recombinant PrP, either containing copper (holo-PrP) or devoid of it (apo-PrP), on plasminogen activation by both uPA and tPA was determined. PrP had no effect on plasminogen activation by uPA. By contrast, the activity of tPA was stimulated by up to 280-fold. This was observed only with the apo-PrP isoforms. The copper-binding octapeptide repeat region of PrP was involved in the effects, as a mutant lacking this region failed to stimulate plasminogen activation, although a synthetic peptide corresponding to this region was unable to stimulate tPA activity. Competition experiments demonstrated that, in addition to plasminogen binding, the stimulation required a high-affinity interaction between tPA and PrP (K(d) < 2.5 nM). Kinetic analysis revealed a template mechanism for the stimulation, suggesting independent binding sites for tPA and plasminogen. Lack of copper-binding may be an early event in the conversion of PrP(C) to PrP(Sc), and our data therefore suggest that tPA-catalyzed plasminogen activation may provide the basis for a sensitive detection system for the early stages of prion diseases and also play a role in the pathogenesis of these diseases.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Ellis V,Daniels M,Misra R,Brown DRdoi
10.1021/bi025676gsubject
Has Abstractpub_date
2002-06-04 00:00:00pages
6891-6issue
22eissn
0006-2960issn
1520-4995pii
bi025676gjournal_volume
41pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Tyr71 is an invariant residue in all known sequences of tyrosine phenol-lyase (TPL). The substitution of Tyr71 in TPL by phenylalanine results in a mutant Y71F TPL with no detectable activity (greater than 3 x 10(5)-fold reduction) for beta-elimination of L-tyrosine. Y71F TPL can react with S-alkylcysteines, but these...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00038a023
更新日期:1995-09-26 00:00:00
abstract::Pseudomonas aeruginosa PA4872 was identified by sequence analysis as a structurally and functionally novel member of the PEP mutase/isocitrate lyase superfamily and therefore targeted for investigation. Substrate screens ruled out overlap with known catalytic functions of superfamily members. The crystal structure of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701954p
更新日期:2008-01-08 00:00:00
abstract::Double homeodomain (DUX) proteins are encoded by a family of 3.3-kilobase repeated elements dispersed in the human genome. One of these elements named D4Z4 is found in a tandem repeat array on chromosome 4 that is partially deleted in facioscapulohumeral muscular dystrophy. We have evaluated the trafficking and mobili...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi047992w
更新日期:2005-02-22 00:00:00
abstract::The incorporation of extensively fluorinated, or fluorous, analogues of hydrophobic amino acids into proteins potentially provides the opportunity to modulate the physicochemical properties of proteins in a predictable manner. On the basis of the properties of small fluorocarbon molecules, extensively fluorinated prot...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi901481k
更新日期:2009-11-17 00:00:00
abstract::The gene encoding enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system from an Escherichia coli enzyme I mutant was cloned and sequenced. The mutation was shown to be a guanine to adenine transition resulting in an altered protein in which glycine-338 was replaced by aspartic acid. The enzyme I structur...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952052k
更新日期:1996-01-09 00:00:00
abstract::The folding of the two-domain bacterial chaperone PapD has been studied to develop an understanding of the relationship between individual domain folding and the formation of domain-domain interactions. PapD contains six phenylalanine residues, four in the N-terminal domain and two in the C-terminal domain. To examine...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048614u
更新日期:2004-11-02 00:00:00
abstract::Monoclonal antibodies directed against epitopes on each of the five subunits (alpha, beta, gamma, delta, and epsilon) of the Escherichia coli F1 ATPase (ECF1) have been prepared and used to localize the subunits in the enzyme complex. Fab' fragments, prepared by pepsin digestion of the antibodies, were bound to ECF1 a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00437a031
更新日期:1989-05-30 00:00:00
abstract::The conversion of prion protein (PrP) to the pathogenic PrPSc conformation is central to prion disease. Previous studies revealed that PrP interacts with lipids and the interaction induces PrP conformational changes, yet it remains unclear whether in the absence of any denaturing treatment, PrP-lipid interaction is su...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700299h
更新日期:2007-06-12 00:00:00
abstract::Phosphoprotein particles were isolated in their native state from the physiological fluid of the estuarine clam Rangia cuneata , and the characteristics of the mineral ion-protein complex which constitutes the native particle were investigated by using mineral ion binding and mineral ion exchange techniques. The parti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00302a017
更新日期:1984-03-27 00:00:00
abstract::A chromatin-bound protease, active in 2 M NaCl-5 M urea or 5 M urea alone, was demonstrated in rat liver, kidney, testes, brain, rabbit bone marrow, chicken reticulocyte, and Ehrlich ascites chromatin. Chicken erythrocyte chromatin did not possess any detectable proteolytic activity in salt and urea. The proteolytic a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00646a028
更新日期:1976-01-13 00:00:00
abstract::Cations often deform the structure of regulatory proteins to affect a functional response, but for other protein functions a more passive effect is desired. For instance, it is shown here that in the conductance of Na+ by the gramicidin channel there appears to be no significant structural deformation of either the si...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi961170k
更新日期:1996-09-17 00:00:00
abstract::Proton nuclear magnetic resonance and ultraviolet circular dichroism spectroscopy have been used to probe the conformational ensemble of the tandemly repeating tetrapeptide unit of the circumsporozoite coat protein of the malaria parasite Plasmodium falciparum. Peptides based on the Asn-Ala-Asn-Pro and Asn-Pro-Asn-Ala...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00486a008
更新日期:1990-08-28 00:00:00
abstract::Marijuana is the most widely abused illegal drug, and its spectrum of effects suggests that several receptors are responsible for the activity. Two cannabinoid receptor subtypes, CB1 and CB2, have been identified, but the complex pharmacological properties of exogenous cannabinoids and endocannabinoids are not fully e...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200010k
更新日期:2011-06-28 00:00:00
abstract::The structural behavior of the nucleosome core particles in the range of solvent Na+ concentration from 10.45 to 0.45 mM has been studied by small-angle neutron and synchroton radiation X-ray scattering, sedimentation, atomic absorption spectroscopy, density measurements, and circular dichroism. With decreasing salt c...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00420a051
更新日期:1988-10-04 00:00:00
abstract::Heat shock protein 90 (Hsp90) is a highly conserved ATP-driven machine involved in client protein maturation, folding, and activation. The chaperone is supported by a set of cochaperones that confer client specificities. One of those proteins is the suppressor of G2 allele of skp1 (Sgt1), which participates together w...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi5000542
更新日期:2014-04-22 00:00:00
abstract::The binding of 8-anilino-1-naphthalenesulfonate (ANS) to ciliary dynein ATPase leads to a marked increase in the dye's fluorescence intensity, accompanied by a blue shift in the observed fluorescence emission maximum. We found that dynein has 37 +/- 3 ANS binding sites and that experimentally applied ANS concentration...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00347a012
更新日期:1985-12-17 00:00:00
abstract::The potential of the frequently encountered (βα)8-barrel fold to acquire new functions was tested by an approach combining random mutagenesis and selection in vivo. For this purpose, the genes encoding 52 different phosphate-binding (βα)8-barrel proteins were subjected to error-prone PCR and cloned into an expression ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.9b00579
更新日期:2019-10-15 00:00:00
abstract::The voltage-gated potassium channel, K(v)1.3, is a novel target for development of immunosuppressants. Using a functional (86)Rb(+) efflux assay, a new class of high-affinity K(v)1.3 inhibitors has been identified. The initial active in this series, 4-phenyl-4-[3-(2-methoxyphenyl)-3-oxo-2-azaprop-1-yl]cyclohexanone (P...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi025722c
更新日期:2002-06-18 00:00:00
abstract::Crystallographic analysis revealed that the nicotinamide ring of NAD can bind with multiconformations to aldehyde dehydrogenase (ALDH) (Ni, L., Zhou, J., Hurley, T. D., and Weiner, H. (1999) Protein Sci. 8, 2784-2790). Electron densities can be defined for two conformations, neither of which appears to be compatible w...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi012197t
更新日期:2002-06-04 00:00:00
abstract::Bioluminescence with luciferase-luciferin pairs is an attractive method for surveying cells in live tissues and whole organisms. Recent advances in luciferin chemistry and luciferase engineering are further expanding the scope of the technology. It is now possible to spy on cells in a variety of deep tissues and visua...
journal_title:Biochemistry
pub_type: 杂志文章,评审
doi:10.1021/acs.biochem.7b00435
更新日期:2017-10-03 00:00:00
abstract::The molecular chaperone SecB binds to hydrophobic sections of unfolded secretory proteins and thereby prevents their premature folding prior to secretion by the translocase of Escherichia coli. Here, we have investigated the effect of the single-residue mutation of leucine 42 to arginine (L42R) centrally positioned in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi902051e
更新日期:2010-03-23 00:00:00
abstract::Depletion of Ca2+ and/or Cl- ions from PSII membranes blocks the electron-transfer reactions that precede O2 evolution on the oxidizing side of the enzyme. Illumination of these inhibited preparations at 273 K generates a paramagnetic species that is detectable by low-temperature (T < 20 K) EPR as a signal in the g = ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972980e
更新日期:1998-05-05 00:00:00
abstract::The molecular mass (M(r)) of the nickel- and iron-sulfur-containing enzyme CO dehydrogenase from Clostridium thermoaceticum was determined by sedimentation equilibrium ultracentrifugation to be 300,000 +/- 30,000 Da. Since the enzyme is known to contain equal numbers of two types of subunits (M(r) = 82,000 Da for alph...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9511853
更新日期:1996-02-13 00:00:00
abstract::The ATF (activating transcription factor) binding site within the E2A promoter region of adenovirus is shown to exist in a novel conformation in vitro via nuclear magnetic resonance methods. This novel conformation may be important to the protein DNA recognition process. This conformation has characteristics of both A...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00077a003
更新日期:1993-07-06 00:00:00
abstract::The carbohydrate binding specificity of the seed lectin from Artocarpus integrifolia, artocarpin, has been elucidated by the enzyme-linked lectin absorbent assay [Misquith, S., et al (1994) J. Biol. Chem. 269, 30393-30401], wherein it was demonstrated to be a Man/Glc specific lectin with high affinity for the trisacch...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000744p
更新日期:2000-09-05 00:00:00
abstract::Human type-alpha transforming growth factor (hTGF alpha) is a small mitogenic protein containing 50 amino acids and three disulfide bonds. It has both sequence and structural homology with epidermal growth factor (EGF). While the three-dimensional structures of hTGF alpha and other EGF-like proteins have been studied ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00008a003
更新日期:1995-02-28 00:00:00
abstract::The red pigments in meat products, including cooked cured ham, arise from the reaction of myoglobin with nitric oxide generated from exogenous nitrite. Since carcinogenic nitrosoamines may be generated by the treatment of meats with nitrite, the production of nitrite-free meat products is an attractive alternative. Ra...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701460x
更新日期:2007-12-25 00:00:00
abstract::Typical cytochrome P450s secure the heme prosthetic group with a cysteine thiolate ligand bound to the iron, electrostatic interactions with the heme propionate carboxylates, and hydrophobic interactions with the heme periphery. In addition to these interactions, CYP4B1 covalently binds heme through a monoester link f...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051267j
更新日期:2005-10-25 00:00:00
abstract::Proton NMR studies were conducted on the complementary 15-mer duplex d(5'-TACTCTTCTTGACCT).(5'-AGGTCAAGAAGAGTA) (designated as unmodified 15-mer duplex) spanning a portion of the mouse c-Ha-ras protooncogene centered around codon 61. Identical studies were carried out on the same sequence, after specific modification ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00155a011
更新日期:1992-10-13 00:00:00
abstract::Integrin beta subunits contain a highly conserved I-like domain that is known to be important for ligand binding. Unlike integrin I domains, the I-like domain requires integrin alpha and beta subunit association for optimal folding. Pactolus is a novel gene product that is highly homologous to integrin beta subunits b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi016047u
更新日期:2002-04-02 00:00:00