Abstract:
:We have previously shown functional differences in fibrinogen from hyperhomocysteinemic rabbits compared to that in control rabbits. This acquired dysfibrinogenemia is characterized by fibrin clots that are composed of abnormally thin, tightly packed fibers with increased resistance to fibrinolysis. Homocysteine thiolactone is a metabolite of homocysteine (Hcys) that can react with primary amines. Recent evidence suggests that Hcys thiolactone-lysine adducts form in vivo. We now demonstrate that the reaction of Hcys thiolactone with purified fibrinogen in vitro produces fibrinogen (Hcys fibrinogen) with functional properties that are strikingly similar to those we have observed in homocysteinemic rabbits. Fibrinogen purified from homocysteinemic rabbits and Hcys fibrinogen are similar in that (1) they both form clots composed of thinner, more tightly packed fibers than their respective control rabbit and human fibrinogens; (2) the clot structure could be made to be more like the control fibrinogens by increased calcium; and (3) they both form clots that are more resistant to fibrinolysis than those formed by the control fibrinogens. Further characterization of human fibrinogens showed that Hcys fibrin had similar plasminogen binding to that of the control and an increased capacity for binding tPA. However, tPA activation of plasminogen on Hcys fibrin was slower than that of the control. Mass spectrometric analysis of Hcys fibrinogen revealed twelve lysines that were homocysteinylated. Several of these are close to tPA and plasminogen binding sites. Lysines are major binding sites for fibrinolytic enzymes and are also sites of plasmin cleavage. Thus, modification of lysines in fibrinogen could plausibly lead to impaired fibrinolysis. We hypothesize that the modification of lysine by Hcys thiolactone might occur in vivo, lead to abnormal resistance of clots to lysis, and thereby contribute to the prothrombotic state associated with homocysteinemia.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Sauls DL,Lockhart E,Warren ME,Lenkowski A,Wilhelm SE,Hoffman Mdoi
10.1021/bi052076jsubject
Has Abstractpub_date
2006-02-28 00:00:00pages
2480-7issue
8eissn
0006-2960issn
1520-4995journal_volume
45pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Decarboxylation reactions from comparable thiamin diphosphate- and thiamin-derived adducts of p-(halomethyl)benzoylformic acids in enzymic and non-enzymic reactions, respectively, reveal critical distinctions in otherwise similar Breslow intermediates. The ratio of protonation to chloride elimination from the Breslow ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.9b00298
更新日期:2019-08-27 00:00:00
abstract::Although the binding of bivalent metal-ion activators to phosphoglucomutase produces substantial changes in the near ultraviolet spectrum of the enzyme, the extent to which aromatic residues are exposed to the aqueous environment, as assessed by means of solvent perturbation spectroscopy (using D2O), does not appear t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00601a031
更新日期:1978-04-18 00:00:00
abstract::Sir2 protein deacetylases (or sirtuins) catalyze NAD+-dependent conversion of epsilon-amino-acetylated lysine residues to deacetylated lysine, nicotinamide, and 2'-O-acetyl-ADP-ribose. Small-molecule modulation of sirtuin activity might treat age-associated diseases, such as type II diabetes, obesity, and neurodegener...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7013294
更新日期:2007-12-18 00:00:00
abstract::Multiple forms of the acute-phase serum protein SAA were isolated from the lipoprotein fraction of plasma from a single individual. These protein forms were purified by size-exclusion, ion-exchange, and reverse-phase high-pressure liquid chromatography, and then the tryptic peptides were subjected to amino acid sequen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00405a044
更新日期:1988-03-08 00:00:00
abstract::The anomeric proton (H-1) chemical shifts of D-mannopyranosides in aqueous solution are affected both by the aglycon and by substitution of the ring [Lee, Y. C., & Ballou, C. E. (1965) Biochemistry 4, 257]. We have examined the 1H NMR spectra for a variety of linear and branched mannooligosaccharides and have assigned...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00559a031
更新日期:1980-09-02 00:00:00
abstract::Unoccupied estrogen receptor (ER) can be extracted from tissues by homogenization with a hypotonic buffer, whereas hormone-occupied ER becomes tightly bound to the nuclear pellet and must be extracted with high-salt-containing buffers. The molecular basis for estrogen-induced tight nuclear binding of ER remains an imp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982190k
更新日期:1999-06-01 00:00:00
abstract::The recently isolated Escherichia coli murB gene (Pucci et al., 1992) has been cloned into an expression vector and the encoded UDP-N-acetylenolpyruvylglucosamine reductase (EC 1.1.1.158) was overproduced to about 10% of soluble cell protein. The encoded 38-kDa protein has been purified to near homogeneity. It was fou...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00059a019
更新日期:1993-03-02 00:00:00
abstract::All eight cysteine residues, C90, C94, C143, C147, C219, C325, C367, and C431, present in transmembrane domains of the Aspergillus nidulans NrtA nitrate transporter protein were altered individually by site-specific mutagenesis. The results indicate that six residues, C90, C147, C219, C325, C367, and C431, are not req...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi047732e
更新日期:2005-04-12 00:00:00
abstract::Detailed analysis of factors governing high affinity antibody-antigen interactions yields important insight into molecular recognition and facilitates the design of functional antibody libraries. Here we describe comprehensive mutagenesis of the light chain complementarity determining regions (CDRs) of HIV-1 antibody ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100293q
更新日期:2010-07-06 00:00:00
abstract::Previous studies have shown that protein 4.1 is a multifunctional protein that binds to spectrin, actin, glycophorins, the anion channel protein, and phosphatidylserine (PS). In this report, we have characterized the binding of protein 4.1 and its major proteolytic fragments to phospholipid vesicles. Pure 125I-labeled...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00402a018
更新日期:1988-01-26 00:00:00
abstract::The crystal structure of Pseudomonas putida cytochrome P-450cam in the substrate-free form has been refined at 2.20-A resolution and compared to the substrate-bound form of the enzyme. In the absence of the substrate camphor, the P-450cam heme iron atom is hexacoordinate with the sulfur atom of Cys-357 providing one a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00366a049
更新日期:1986-09-09 00:00:00
abstract::Accumulation of the cytotoxic 40- to 42-residue beta-amyloid peptide represents the primary pathological process in Alzheimer's disease (AD). BACE1 (beta-site APP cleaving enzyme 1) is responsible for the initial required step in the neuronal amyloidogenic processing of beta-amyloid precursor protein and is a major dr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051040o
更新日期:2005-12-20 00:00:00
abstract::The effects of ions on the interaction of lac repressor protein and operator DNA have been studied by the membrane filter technique. The equilibrium association constant was determined as a function of monovalent and divalent cation concentrations, anions, and pH. The binding of repressor and operator is extremely sen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00516a027
更新日期:1981-06-23 00:00:00
abstract::Topoisomerase II mediated double-strand breaks produced by anthracycline analogues were studied in SV40 DNA. The compounds included doxorubicin, daunorubicin, two doxorubicin stereoisomers (4'-epimer and beta-anomer), and five chromophore-modified derivatives, with a wide range of cytotoxic activity and DNA binding af...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00454a033
更新日期:1990-01-16 00:00:00
abstract::Postsynaptic polypeptide neurotoxins isolated from the venoms of elapid and hydrophid snakes exhibit the ability to bind selectively to and inhibit different types of receptors that function in nerve signal transmission. On the basis of their amino acid sequences and three-dimensional structures, these neurotoxins are...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00179a011
更新日期:1994-04-05 00:00:00
abstract::The SfiI restriction enzyme binds to DNA as a tetramer holding two usually distant DNA recognition sites together before cleavage of the four DNA strands. To elucidate structural properties of the SfiI-DNA complex, atomic force microscopy (AFM) imaging of the complexes under noncleaving conditions (Ca2+ instead of Mg2...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051767c
更新日期:2006-01-10 00:00:00
abstract::The structure of the ca. 250 amino acid hormone binding domain of the human estrogen receptor (hER-LBD), expressed in E. coli and purified as a complex with estradiol, has been probed by selective proteolysis, with analysis of the protein fragments both by classical methods (SDS-PAGE and Edman N-terminal sequencing) a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00039a016
更新日期:1995-10-03 00:00:00
abstract::Nitroalkane oxidase (NAO) from Fusarium oxysporum catalyzes the oxidation of neutral nitroalkanes to the corresponding aldehydes or ketones with the production of H(2)O(2) and nitrite. The flavoenzyme is a new member of the acyl-CoA dehydrogenase (ACAD) family, but it does not react with acyl-CoA substrates. We presen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051966w
更新日期:2006-01-31 00:00:00
abstract::The kinetics of the tryptophan fluorescence enhancement that occurs when myofibrils (rabbit psoas) are mixed with Mg-ATP were studied by stopped-flow in different solvents (water, 40% ethylene glycol, 20% methanol) at 4 degrees C. Under relaxing conditions (low Ca(2+)) in water (mu = 0.16 M, pH 7.4) and at high ATP co...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0004753
更新日期:2000-06-27 00:00:00
abstract::Rh(phen)2phi3+ (phen = 1,10-phenanthroline; phi = 9,10-phenanthrenequinone diimine) avidly binds to DNA via intercalation from the major groove and upon photoactivation produces strand scission with single base 5' asymmetry. Enantiomers of Rh(phen)2phi3+, which lack hydrogen-bonding substituents in ancillary positions...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00180a005
更新日期:1994-04-12 00:00:00
abstract::Virulent strains of Clostridium sordellii cause gangrenous myonecrosis in humans. The released lethal toxin (TcsL) and hemorrhagic toxin (TcsH) are regarded as the major virulence factors. TcsL inactivates low molecular weight GTP-binding proteins of the Rho/Ras subfamilies by monoglucosylation. In cultured cell lines...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900964c
更新日期:2009-09-29 00:00:00
abstract::Human DNA polymerase kappa (pol kappa) has a sequence significantly homologous with that of Escherichia coli DNA polymerase IV (pol IV). We used a truncated form of human pol kappa (pol kappaDeltaC) and full-length pol IV to explore the miscoding properties of these enzymes. Oligodeoxynucleotides, modified site-specif...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010702g
更新日期:2001-12-18 00:00:00
abstract::Pantothenate synthetase (PS, EC 6.3.2.1) is the last enzyme in the pantothenate biosynthesis pathway, a metabolic pathway identified as a potential target for new antimicrobials. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Here we report the overexpression, purificati...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi1004206
更新日期:2010-08-03 00:00:00
abstract::PhnZ utilizes a mixed valence diiron(II/III) cofactor and O2 to oxidatively cleave the carbon-phosphorus bond of (R)-2-amino-1-hydroxyethylphosphonic acid to form glycine and orthophosphate. The active site residues Y24 and E27 are proposed to mediate induced-fit recognition of the substrate and access of O2 to one of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.9b00145
更新日期:2019-12-31 00:00:00
abstract::We have examined proteins containing the DNA-binding domain of c-Myb with biophysical methods. This DNA-binding domain consists of three imperfect repeats (R1, R2, and R3) conserved among many species. Our results indicate that the DNA-binding domain forms unspecific and specific complexes with oligodeoxynucleotides. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00252a026
更新日期:1994-12-06 00:00:00
abstract::Sedimentation in a preparative ultracentrifuge was used to determine the affinity of heavy meromyosin, HMM, for regulated actin, F-actin plus troponin-tropomyosin, in the presence of MgATP at pH 7.0, 20 degrees C, and mu = 18 mM. HMM was prepared from vertebrate striated muscle myosin by a mild chymotryptic digestion....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00275a003
更新日期:1983-03-15 00:00:00
abstract::We find that the photocycle of halorhodopsin (HR) in the presence of nitrate (but not chloride) consists of two parallel series of reactions. The first is essentially the same as that which occurs in the presence of chloride: HRhv----HRK----HRKL----HRL----HRO----HR. The second photocycle, however, which we describe as...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00438a039
更新日期:1989-06-13 00:00:00
abstract::The Escherichia coli Ada protein repairs methylphosphotriesters in DNA through direct, irreversible transfer to a cysteine residue on the protein, Cys 69. Methylation of Cys 69 increases the sequence-specific DNA-binding activity of Ada by 10(3)-fold, enabling the methylated protein to activate transcription of a meth...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi011001m
更新日期:2001-09-25 00:00:00
abstract::Human lung tryptase (HLT), a trypsin-like serine proteinase stored as an active enzyme in association with heparin in mast cell granules, is released into the extracellular environment when mast cells are activated. Tryptases are unusual in that they form tetramers and bind heparin. As there are no known endogenous tr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960042t
更新日期:1996-10-22 00:00:00
abstract::Toxic shock syndrome toxin-1 (TSST-1), the potent staphylococcal exoprotein linked to most cases of the toxic shock syndrome, is a V beta-restricted T-cell mitogen (a so-called "superantigen"). TSST-ovine (TSST-O) is a natural variant of TSST-1, and is produced by certain ovine mastitis-associated strains of Staphyloc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00209a016
更新日期:1994-11-01 00:00:00