Abstract:
:Alzheimer's disease (AD) paired helical filaments (PHFs), building blocks of neurofibrillary tangles (NFTs) are composed of hyperphosphorylated forms of the microtubule-associated protein tau (i.e., PHF-tau). Currently, much effort is devoted to the development of diagnostic antibodies specific for PHF-tau since elevated tau levels are found in the cerebral spinal fluid of AD patients. To this end, we have mapped the epitopes of a large panel of monoclonal antibodies (mAbs) that recognized only phosphorylation dependent epitopes on PHF-tau. These mAbs include the PHF-tau specific mAb AT10 and 12 newly developed anti-PHF mAbs that recognize PHF-tau but not autopsy-derived normal adult tau on Western-blot and enzyme-linked immunosorbent assay (ELISA). Epitope analysis, together with data on known binding sites of previously published mAbs, revealed that Ser214, Thr231, and Ser396 are immunodominant phosphorylated amino acids in PHF-tau. Six of the 12 new mAbs recognized one of these three phosphorylated sites. With the exception of AT10 and PHF-27, all the mAbs also labeled fetal tau and biopsy-derived tau. Since mAbs AT10 and PHF-27 had little or no affinity for fetal tau and biopsy tau, they can be considered as the first "true" PHF-specific antibodies capable of distinguishing tau isoforms from normal versus AD subjects, suggesting a possible utility of these mAbs as diagnostic markers. Remarkably, the true PHF-specific antibodies recognized peptide sequences phosphorylated on more than one amino acid residue. The peptide recognition of mAb AT10 required the simultaneous phosphorylation of Thr212 and Ser214, and the peptide recognition of mAb PHF-27 was markedly increased when both the primary site Thr231 and the subsite Ser235 were phosphorylated. Since AT10 and PHF-27 are the only mAbs currently available that bind specifically to PHF-tau, these data suggest that double phosphorylation at Thr212/Ser214 and Thr231/Ser235 may be unique to PHF-tau. These data may facilitate the development of mAbs that can be used as specific diagnostic reagents for the detection of altered tau in cerebrospinal fluid of AD patients.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Hoffmann R,Lee VM,Leight S,Varga I,Otvos L Jrdoi
10.1021/bi970380+subject
Has Abstractpub_date
1997-07-01 00:00:00pages
8114-24issue
26eissn
0006-2960issn
1520-4995pii
bi970380+journal_volume
36pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Escherichia coli 3-methyladenine DNA glycosylase II (AlkA), an adaptive response glycosylase with a broad substrate range, initiates base excision repair by flipping a lesion out of the DNA duplex and hydrolyzing the N-glycosidic bond. We used transient and steady state kinetics to determine the minimal mechanism for ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi501356x
更新日期:2015-01-27 00:00:00
abstract::The structural protein nonerythroid alpha spectrin (alphaIISp) plays a role in the repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), in which there is a defect in ability to repair such cross-links. We have proposed a model in which alphaIISp, whose stability is de...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi801483u
更新日期:2009-01-20 00:00:00
abstract::Arginase is a binuclear Mn(2+) metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. X-ray crystal structures of arginase complexed to substrate analogues N(omega)-hydroxy-L-arginine and N(omega)-hydroxy-nor-L-arginine, as well as the products L-ornithine and urea, complete a set of struct...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002318+
更新日期:2001-03-06 00:00:00
abstract::N-linked, high-mannose-type oligosaccharides lacking glucose residues may be transiently glucosylated directly from UDP-Glc in the endoplasmic reticulum of mammalian, plant, fungal, and protozoan cells. The products formed have been identified as N-linked Glc1Man5-9GlcNAc2 and glucosidase II is apparently the enzyme r...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00226a017
更新日期:1991-03-26 00:00:00
abstract::Drosophila Rrp1 includes a carboxy-terminal region homologous to Escherichia coli exonuclease III which is sufficient to repair both oxidative and alkylation damage to DNA. An apurinic/apyrimidinic endonuclease activity intrinsic to Rrp1 was characterized previously. In this work, the 3'-phosphodiesterase and 3'-phosp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00004a021
更新日期:1995-01-31 00:00:00
abstract::myo-Inositol (mI) is widely distributed in all domains of life and is important for several cellular functions, including bacterial survival. The enzymes responsible for the bacterial catabolism of mI, encoded in the iol operon, can vary from one organism to another, and these pathways have yet to be fully characteriz...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.0c00539
更新日期:2020-08-18 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) is an intracellular receptor protein that regulates gene transcription in response to both man-made and natural ligands. A modular transactivaton domain (TAD) has been mapped to the 304 C-terminal amino acids and consists of acidic, Q-rich, and P/S/T-rich subdomains. We have used st...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0487701
更新日期:2005-01-18 00:00:00
abstract::The aminolysis of the depsipeptide m-[[(phenylacetyl)glycyl]oxy]benzoic acid (1) by D-phenylalanine, catalyzed by the beta-lactamase of Enterobacter cloacae P99, is inhibited by the product of the reaction, (phenylacetyl)glycyl-D-phenylalanine (2), by the peptide analogue of 1, m-[(phenylacetyl)-glycinamido]benzoic ac...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00443a015
更新日期:1989-08-22 00:00:00
abstract::A high molecular weight acyl coenzyme A (acyl-CoA) thioesterase, designated thioesterase II, has been purified 5300-fold from photoheterotrophically grown cells of Rhodopseudomonas sphaeroides. In contrast to R. sphaeroides acyl-CoA thioesterase I [Boyce, S.G., & Lueking, D.R. (1984) Biochemistry 23, 141-147], thioest...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00357a029
更新日期:1986-05-06 00:00:00
abstract::We have developed a model of glycophorin in a phospholipid bilayer membrane in order to study the thermodynamics of this system and to understand the detailed behavior of recent calorimetric data. We assume that the larger glycophorin polar group can be considered as either adopting a pancakelike conformation at the b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00381a019
更新日期:1987-04-07 00:00:00
abstract::L6 is a monoclonal antitumor antibody which recognizes an epitope located in a 42-residue extracellular domain of a tumor-associated approximately 22 kDa glycoprotein antigen. The L6 mAb localizes to solid tumors in vivo and triggers complement activation and antibody-dependent cellular cytotoxicity. It has been the s...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00252a005
更新日期:1994-12-06 00:00:00
abstract::Firefly luciferase is 80-90% inactivated within 3 h upon incubation with the adenine nucleotide analogue p-fluorosulfonylbenzoyl-5'-adenosine (FSBA). Although 4 mol of 14C-FSBA/mol of enzyme is irreversibly bound during inactivation, only 1 mol of 14C-FSBA appears to be specifically directed to an adenine nucleotide b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00508a031
更新日期:1981-03-03 00:00:00
abstract::RP2 is a ubiquitously expressed protein encoded by a gene associated with X-linked retinitis pigmentosa (XLRP), a retinal degenerative disease that causes severe vision loss. Previous in vitro studies have shown that RP2 binds to ADP ribosylation factor-like 3 (Arl3) and activates its intrinsic GTPase activity, but th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi1005249
更新日期:2010-09-07 00:00:00
abstract::It is known that aconitase from mammalian mitochondria is only partially active as isolated but may be activated by incubation with iron, ascorbate, and a thiol, or with dithionite. It has been suggested that the added Fe in the activation mixture is essential for activation and that it is incorporated in the enzyme [...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00529a023
更新日期:1981-12-22 00:00:00
abstract::The interaction of the recombinant hemoglobin from Vitreoscilla sp. (VHb) with the bacterial membrane of Escherichia coli cells has been investigated by measuring the propensity of VHb to interact with monolayers formed by natural bacterial phosholipids. The measurements showed that the protein is capable of penetrati...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi052277n
更新日期:2006-04-04 00:00:00
abstract::In this work, we show that adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) is a substrate for yeast inorganic pyrophosphatase (PPase) (EC 3.6.1.1) and further, using chirally labeled [gamma-17O,18O]ATP gamma S, that enzyme-catalyzed hydrolysis to produce chiral inorganic thio[17O,18O]phosphate proceeds with inversio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00300a002
更新日期:1984-02-28 00:00:00
abstract::CC chemokine receptor 5 (CCR5) is the receptor for several inflammatory chemokines and is a coreceptor for HIV-1. Posttranslational sulfation of tyrosines in the N-terminal regions of chemokine receptors has been shown to be important in the binding affinity for chemokine ligands. In addition, sulfation of CCR5 is cru...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900285c
更新日期:2009-06-16 00:00:00
abstract::The human intestinal Caco-2 cell line, described as enterocyte-like in a number of studies, was examined for its ability to carry out the metabolism of vitamin A normally required in the absorptive process. Caco-2 cells contained cellular retinol-binding protein II, a protein which is abundant in human villus-associat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00502a015
更新日期:1990-12-18 00:00:00
abstract::NSC 613862 (S)-(-) and NSC 613863 (R)-(+) are the two chiral isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3, 4-b]pyrazin-7-yl carbamate. Both compounds bind to tubulin in a region that overlaps the colchicine site. They induce formation of abnormal polymers from purified GTP-Mg-tubulin, the active asse...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970568t
更新日期:1998-01-13 00:00:00
abstract::Pokeweed antiviral protein (PAP) is a single-chain ribosome inactivating protein (RIP) that binds to ribosomes and depurinates the highly conserved alpha-sarcin/ricin loop (SRL) of the large subunit rRNA. Catalytic depurination of a specific adenine has been proposed to result in translation arrest and cytotoxicity. H...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048188c
更新日期:2005-02-22 00:00:00
abstract::Vangl1 and Vangl2 are membrane proteins that play an important role in neurogenesis, and Vangl1/Vangl2 mutations cause neural tube defects in mice and humans. At the cellular level, Vangl proteins regulate the establishment of planar cell polarity (PCP), a process requiring membrane assembly of asymmetrically distribu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101767a
更新日期:2011-03-29 00:00:00
abstract::An important but poorly characterized contribution to the thermodynamics of protein-DNA interactions is the loss of entropy that occurs from restricting the conformational freedom of amino acid side chains. The effect of restricting the flexibility of several side chains at a protein-DNA interface may be comparable in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00195
更新日期:2018-05-15 00:00:00
abstract::Vesicular stomatitis virus buds from domains of the plasma membrane that have a unique protein and lipid composition. Fluorescence digital imaging microscopy and resonance energy transfer were used to determine how the two viral envelope-associated proteins, the G and the M proteins, could alter the lateral distributi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00031a008
更新日期:1995-08-08 00:00:00
abstract::ZntA from Escherichia coli confers resistance to toxic concentrations of Pb2+, Zn2+, and Cd2+. It is a member of the P1B-ATPase transporter superfamily, which includes the human Cu+-transporting proteins ATP7A and ATP7B. P1B-type ATPases typically have a hydrophilic N-terminal metal-binding domain and eight transmembr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.0c00770
更新日期:2020-12-01 00:00:00
abstract::Translocator protein 18 kDa (TSPO) was previously known as the peripheral benzodiazepine receptor (PBR) in eukaryotes, where it is mainly localized to the mitochondrial outer membrane. Considerable evidence indicates that it plays regulatory roles in steroidogenesis and apoptosis and is involved in various human disea...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00142
更新日期:2016-05-24 00:00:00
abstract::The R2 protein of ribonucleotide reductase catalyzes the dioxygen-dependent one-electron oxidation of Tyr122 at a diiron-carboxylate site. Methane monooxygenase and related hydroxylases catalyze hydrocarbon hydroxylation at diiron sites structurally related to the one in R2. In protein R2, the likely reaction site for...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9806403
更新日期:1998-07-28 00:00:00
abstract::The structural domains of human apolipoprotein(a) [apo(a)] and its interaction with apolipoprotein B-100 (apo B-100) in the lipoprotein(a) [Lp(a)] particle were investigated by limited proteolysis with thermolysin and cathepsin D. We characterized the proteolytic products by sodium dodecyl sulfate-polyacrylamide gradi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00177a026
更新日期:1994-03-22 00:00:00
abstract::Tec family nonreceptor tyrosine kinases are key immunological enzymes that control processes that range from T and B cell development to reorganization of the actin cytoskeleton. The full-length Tec kinases have been resistant to crystallization. This lack of structural data and the paucity of in vitro biochemical dat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi602512e
更新日期:2007-05-08 00:00:00
abstract::Complementary DNA clones coding for the human secreted carbonic anhydrase isozyme (CA VI) have been isolated and their nucleotide sequences determined. These clones identify a 1.45-kb mRNA that is present in high levels in parotid submandibular salivary glands but absent in other tissues such as the sublingual gland, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00216a035
更新日期:1991-01-15 00:00:00
abstract::Xylose isomerase (E.C. 5.3.1.5) catalyzes the interconversion of aldose and ketose sugars and has an absolute requirement for two divalent cations at its active site to drive the hydride transfer rates of sugar isomerization. Evidence suggests some degree of metal movement at the second metal site, although how this m...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049812o
更新日期:2004-06-01 00:00:00