Search results for "SUBSTRATE"
showing 10 items of 1018 documents
Kinetic experiments on the binding of metyrapone to liver microsomes
1969
Kinetic experiments on the inhibition of oxidative microsomal O- and N-demethylations by metyrapone (2-methyl-1, 2-bis(3-pyridyl)-l-propanone, Su 4885) were carried out using mouse liver microsomes as the enzyme source. The model substrates were p-nitroanisole and N-monomethyl-p-nitroaniline. It was shown that the inhibition is competitive. The K i for metyrapone is 0.42 × 10−4 M and for the reduced metabolite of metyrapone 1.15×10−4 M. Their spectral dissooiation constants as determined from difference spectra have almost the same values. From this it is concluded that the degree of inhibition is correlated to the amount of metyrapone bound to cytochrome P-450. Metyrapone does not seem to …
All-Atom simulations disclose how cytochrome reductase reshapes the substrate access/egress routes of its partner cyp450s
2020
Cytochromes P450 enzymes (CYP450s) promote the oxidative metabolism of a variety of substrates via the electrons supplied by the cytochrome P450 reductase (CPR) and upon formation of a CPR/CYP450 adduct. In spite of the pivotal regulatory importance of this process, the impact of CPR binding on the functional properties of its partner CYP450 remains elusive. By performing multiple microsecond-long all-Atom molecular dynamics simulations of a 520â »000-Atom model of a CPR/CYP450 adduct embedded in a membrane mimic, we disclose the molecular terms for their interactions, considering the aromatase (HA) enzyme as a proxy of the CYP450 family. Our study strikingly unveils that CPR binding alters…
Availability of O 2 as a Substrate in the Cytoplasm of Bacteria under Aerobic and Microaerobic Conditions
1998
ABSTRACT The growth rates of Pseudomonas putida KT2442 and mt-2 on benzoate, 4-hydroxybenzoate, or 4-methylbenzoate showed an exponential decrease with decreasing oxygen tensions (partial O 2 tension [pO 2 ] values). The oxygen tensions resulting in half-maximal growth rates were in the range of 7 to 8 mbar of O 2 (corresponding to 7 to 8 μM O 2 ) (1 bar = 10 5 Pa) for aromatic compounds, compared to 1 to 2 mbar for nonaromatic compounds like glucose or succinate. The decrease in the growth rates coincided with excretion of catechol or protocatechuate, suggesting that the activity of the corresponding oxygenases became limiting. The experiments directly establish that under aerobic and micr…
Interaction of Mitogen-activated Protein Kinases with the Kinase Interaction Motif of the Tyrosine Phosphatase PTP-SL Provides Substrate Specificity …
1999
ERK1 and ERK2 associate with the tyrosine phosphatase PTP-SL through a kinase interaction motif (KIM) located in the juxtamembrane region of PTP-SL. A glutathione S-transferase (GST)-PTP-SL fusion protein containing the KIM associated with ERK1 and ERK2 as well as with p38/HOG, but not with the related JNK1 kinase or with protein kinase A or C. Accordingly, ERK2 showed in vitro substrate specificity to phosphorylate GST-PTP-SL in comparison with GST-c-Jun. Furthermore, tyrosine dephosphorylation of ERK2 by the PTP-SLDeltaKIM mutant was impaired. The in vitro association of ERK1/2 with GST-PTP-SL was highly stable; however, low concentrations of nucleotides partially dissociated the ERK1/2.P…
The sequence alteration associated with a mutational hotspot in p53 protects cells from lysis by cytotoxic T lymphocytes specific for a flanking pept…
1998
A high proportion of tumors arise due to mutation of the p53 tumor suppressor protein. A p53 hotspot mutation at amino acid position 273 from R to H, flanking a peptide epitope that spans residues 264–272, renders cells resistant to killing by human histocompatibility leukocyte antigen (HLA)-A*0201–restricted cytotoxic T lymphocytes (CTLs) specific for this epitope. Acquisition of the R to H mutation at residue 273 of the human p53 protein promotes tumor growth in vivo by selective escape from recognition by p53.264–272 peptide-specific CTLs. Synthetic 27-mer p53 polypeptides covering the antigenic nonamer region 264–272 of p53 were used as proteasome substrates to investigate whether the R…
A liquid alkoxide precursor for the atomic layer deposition of aluminum oxide films
2020
For large-scale atomic layer deposition (ALD) of alumina, the most commonly used alkyl precursor trimethylaluminum poses safety issues due to its pyrophoric nature. In this work, the authors have investigated a liquid alkoxide, aluminum tri-sec-butoxide (ATSB), as a precursor for ALD deposition of alumina. ATSB is thermally stable and the liquid nature facilitates handling in a bubbler and potentially enables liquid injection toward upscaling. Both thermal and plasma enhanced ALD processes are investigated in a vacuum type reactor by using water, oxygen plasma, and water plasma as coreactants. All processes achieved ALD deposition at a growth rate of 1-1.4 angstrom/cycle for substrate tempe…
UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles
2006
The DNA glycosylase hOGG1 initiates base excision repair (BER) of oxidised purines in cellular DNA. Using confocal microscopy and biochemical cell fractionation experiments we show that, upon UVA irradiation of human cells, hOGG1 is recruited from a soluble nucleoplasmic localisation to the nuclear matrix. More specifically, after irradiation, hOGG1 forms foci colocalising with the nuclear speckles, organelles that are interspersed between chromatin domains and that have been associated with transcription and RNA-splicing processes. The use of mutant forms of hOGG1 unable to bind the substrate showed that relocalisation of hOGG1 does not depend on the recognition of the DNA lesion by the en…
Alteration of nuclear (2'-5')oligoriboadenylate synthetase and nuclease activities preceding replication of human immunodeficiency virus in H9 cells.
1988
After infection of the respective target cells with the human immunodeficiency virus (HIV-1) viral progeny is produced only after a short temporary delay of some days, depending on cell type. After this period of time a sudden onset of HIV-1 protein synthesis with a dramatic increase in virus release occurs. (2'-5')Oligoriboadenylates [(2'-5')A], capable to activate a latent ribonuclease (RNase L) degrading both mRNA and rRNA, are known mediators involved in the early response of cells to virus infection. Here we show that the (2'-5')A-synthesizing (2'-5')A synthetase, which is inducible by interferon and activated by double-stranded RNA, as well as a (2'-5')A nuclease (2',3'-exoribonucleas…
NLRP3 controls ATM activation in response to DNA damage
2020
The DNA damage response (DDR) is essential to preserve genomic integrity and acts as a barrier to cancer. The ATM pathway orchestrates the cellular response to DNA double strand breaks (DSBs), and its attenuation is frequent during tumorigenesis. Here, we show that NLRP3, a Pattern Recognition Receptor known for its role in the inflammasome complex formation, interacts with the ATM kinase to control the early phase of DDR, independently of its inflammasome activity. NLRP3 down-regulation in human bronchial epithelial cells impairs ATM pathway activation as shown by an altered ATM substrate phosphorylation profile, and due to impaired p53 activation, confers resistance to acute genomic stres…
Gene Cloning, Transcriptional Analysis, Purification, and Characterization of Phenolic Acid Decarboxylase from Bacillus subtilis
1998
Phenolic acids, also called substituted cinnamic acids, are important lignin-related aromatic acids and natural constituents of plant cell walls. These acids (particularly ferulic, p-coumaric, and caffeic acids) bind the complex lignin polymer to the hemicellulose and cellulose in plants (1) or are generally esterified with tartaric acid (for example, in grape must, wine, and cider) and can be released as free acids during wine making by some cinnamoyl esterase activities (9). Most often, free phenolic acids are metabolized by different microorganisms into 4-vinyl derivatives and then are eventually reduced into 4-ethyl derivatives (5, 6). Some of these volatile phenols, particularly vinyl …