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71.
Baerga-Ortiz A Bergqvist S Mandell JG Komives EA 《Protein science : a publication of the Protein Society》2004,13(1):166-176
Thrombin binds thrombomodulin (TM) at anion binding exosite 1, an allosteric site far from the thrombin active site. A monoclonal antibody (mAb) has been isolated that competes with TM for binding to thrombin. Complete binding kinetic and thermodynamic profiles for these two protein-protein interactions have been generated. Binding kinetics were measured by Biacore. Although both interactions have similar K(D)s, TM binding is rapid and reversible while binding of the mAb is slow and nearly irreversible. The enthalpic contribution to the DeltaG(bind) was measured by isothermal titration calorimetry and van't Hoff analysis. The contribution to the DeltaG(bind) from electrostatic steering was assessed from the dependence of the k(a) on ionic strength. Release of solvent H(2)O molecules from the interface was assessed by monitoring the decrease in amide solvent accessibility at the interface upon protein-protein binding. The mAb binding is enthalpy driven and has a slow k(d). TM binding appears to be entropy driven and has a fast k(a). The favorable entropy of the thrombin-TM interaction seems to be derived from electrostatic steering and a contribution from solvent release. The two interactions have remarkably different thermodynamic driving forces for competing reactions. The possibility that optimization of binding kinetics for a particular function may be reflected in different thermodynamic driving forces is discussed. 相似文献
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Morandat S Bortolato M Anker G Doutheau A Lagarde M Chauvet JP Roux B 《Biochimica et biophysica acta》2003,1616(2):137-146
Oxidative stress results from the attack by free radicals of several cellular targets (proteins, DNA and lipids). The cell equilibrium is a direct consequence of the pro-/antioxidant balance. In order to understand the physiological processes involved in oxidative stress, we followed oxidation of unsaturated lipids using a biomimetic system: Langmuir monolayers. The oxidation mode chosen was UV-irradiation and the lipid model was a polyunsaturated phospholipid: 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC). The monomolecular film technique was used to measure membrane rheology before and after UV-irradiation. We showed that the UV-irradiation of a DLPC monomolecular film led to a molecular area and surface elasticity modulus decrease that attests to the apparition of new molecular species at the air-water interface. The antioxidant effect of a synthetic plasmalogen (1-O-(1'-(Z)-hexadecenyl)-2-O-oleoyl-sn-glycero-3-phosphocholine or P(PLM)OPE) was tested on the oxidation of DLPC. Indeed, for about 25% mol P(PLM)OPE in mixed DLPC/P(PLM)OPE monolayers, a complete inhibition of the molecular area and the surface elasticity modulus decreases was observed in our experimental conditions. Lower P(PLM)OPE quantities delayed but did not prevent the DLPC oxidation in mixed monolayers. 相似文献
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FQR1, a novel primary auxin-response gene, encodes a flavin mononucleotide-binding quinone reductase 总被引:1,自引:0,他引:1
FQR1 is a novel primary auxin-response gene that codes for a flavin mononucleotide-binding flavodoxin-like quinone reductase. Accumulation of FQR1 mRNA begins within 10 min of indole-3-acetic acid application and reaches a maximum of approximately 10-fold induction 30 min after treatment. This increase in FQR1 mRNA abundance is not diminished by the protein synthesis inhibitor cycloheximide, demonstrating that FQR1 is a primary auxin-response gene. Sequence analysis reveals that FQR1 belongs to a family of flavin mononucleotide-binding quinone reductases. Partially purified His-tagged FQR1 isolated from Escherichia coli catalyzes the transfer of electrons from NADH and NADPH to several substrates and exhibits in vitro quinone reductase activity. Overexpression of FQR1 in plants leads to increased levels of FQR1 protein and quinone reductase activity, indicating that FQR1 functions as a quinone reductase in vivo. In mammalian systems, glutathione S-transferases and quinone reductases are classified as phase II detoxification enzymes. We hypothesize that the auxin-inducible glutathione S-transferases and quinone reductases found in plants also act as detoxification enzymes, possibly to protect against auxin-induced oxidative stress. 相似文献
77.
von Woedtke T Jülich WD Hartmann V Stieber M Abel PU 《Biosensors & bioelectronics》2002,17(5):373-382
A useful method of enzyme glucose sensor sterilization has not only to ensure the needs of sterility assurance but has also to guarantee the functional stability of the sensors. The action of 2 or 3% alkalinized glutaraldehyde solution, as well as gamma irradiation with a dose of 25 kGy caused changes of the in vitro functionality and polymer material irritations, respectively. After a combined treatment by 0.6% hydrogen peroxide solution acting over 4 days with 7 kGy gamma irradiation only a slight loss of sensitivity must be registered. The combination of a specially designed universal homogeneous ultraviolet irradiation over 300 s with a 3 days lasting treatment by an inclusion compound of hydrogen peroxide with tensides in urea (0.15% effective hydrogen peroxide concentration) did not cause any influence on the glucose sensor function in vitro. With all methods tested here, a Bacillus subtilis spore reduction over 8 log(10) cycles from 10(6) to 10(-2) spores per test object on an average could be proved experimentally. In general, if non-thermal methods must be used it seems to be impossible to guarantee a sterility assurance level of 10(-6) as it is demanded by the pharmacopoeias. Consequently, effective concepts to produce sterile glucose biosensors for medical and biological applications should be based not only on final product treatments but should include germ reducing measures in every manufacturing step. 相似文献
78.
The increasing number of complete and nearly complete metazoan genome sequences provides a significant amount of material for large-scale comparative genomic analysis. Finding new effective methods to analyse such enormous datasets has been the object of intense research. Three main areas in comparative genomics have recently shown important developments: whole-genome alignment, gene prediction and regulatory-region prediction. Each of these areas improves the methods of deciphering long genomic sequences and uncovering what lies hidden in them. 相似文献
79.
Santamaría A Flores-Escartín A Martínez JC Osorio L Galván-Arzate S Pedraza-Chaverrí J Chaverrí JP Maldonado PD Medina-Campos ON Jiménez-Capdeville ME Manjarrez J Ríos C 《Free radical biology & medicine》2003,35(4):418-427
Reactive oxygen species and oxidative stress are involved in quinolinic acid (QUIN)-induced neurotoxicity. QUIN, a N-methyl-D-aspartate receptor (NMDAr) agonist and prooxidant molecule, produces NMDAr overactivation, excitotoxic events, and direct reactive oxygen species formation. Copper is an essential metal exhibiting both modulatory effects on neuronal excitatory activity and antioxidant properties. To investigate whether this metal is able to counteract the neurotoxic and oxidative actions of QUIN, we administered copper (as CuSO(4)) intraperitoneally to rats (2.5, 5.0, 7.5, and 10.0 mg/kg) 30 min before the striatal infusion of 1 microliter of QUIN (240 nmol). A 5.0 mg/kg CuSO(4) dose significantly increased the copper content in the striatum, reduced the neurotoxicity measured both as circling behavior and striatal gamma-aminobutyric acid (GABA) depletion, and blocked the oxidative injury evaluated as striatal lipid peroxidation (LP). In addition, copper reduced the QUIN-induced decreased striatal activity of Cu,Zn-dependent superoxide dismutase, and increased the ferroxidase activity of ceruloplasmin in cerebrospinal fluid from QUIN-treated rats. However, copper also produced significant increases of plasma lactate dehydrogenase activity and mortality at the highest doses employed (7.5 and 10.0 mg/kg). These results show that at low doses, copper exerts a protective effect on in vivo QUIN neurotoxicity. 相似文献
80.
Santamaría A Pérez-Severiano F Rodríguez-Martínez E Maldonado PD Pedraza-Chaverri J Ríos C Segovia J 《Neurochemical research》2001,26(4):419-424
We examined the activity of striatal superoxide dismutase (SOD) in two acute pharmacological models of Huntington's disease (HD), and compared it with SOD activity in the striata of mice transgenic for the HD mutation. Total SOD, and Cu/ZnSOD activities increased in young transgenic mice, but decreased in older (35 week) mice. We consider that the increased enzyme activity represents a compensatory mechanism to protect cells from free radical-induced damage, but the system becomes insufficient in older animals. Major decreases in SOD activity were also observed both after quinolinic acid and 3-nitropropionic acid intrastriatal injections. The present results indicate that in both types of HD models striatal oxidative damage occurs, and that it is associated with alterations in the cellular antioxidant system. 相似文献