Abstract：
:The c-Jun N-terminal kinases (JNKs) play a wide variety of roles in cellular signaling processes, dictating important, and even divergent, cellular fates. These essential kinases possess docking surfaces distal to their active sites that interact with diverse binding partners, including upstream activators, downstream substrates, and protein scaffolds. Prior studies have suggested that the interactions of certain protein-binding partners with one such JNK docking surface, termed the D-recruitment site (DRS), can allosterically influence the conformational state of the ATP-binding pocket of JNKs. To further explore the allosteric relationship between the ATP-binding pockets and DRSs of JNKs, we investigated how the interactions of the scaffolding protein JIP1, as well as the upstream activators MKK4 and MKK7, are allosterically influenced by the ATP-binding site occupancy of the JNKs. We show that the affinity of the JNKs for JIP1 can be divergently modulated with ATP-competitive inhibitors, with a >50-fold difference in dissociation constant observed between the lowest- and highest-affinity JNK1-inhibitor complexes. Furthermore, we found that we could promote or attenuate phosphorylation of JNK1's activation loop by MKK4 and MKK7, by varying the ATP-binding site occupancy. Given that JIP1, MKK4, and MKK7 all interact with JNK DRSs, these results demonstrate that there is functional allostery between the ATP-binding sites and DRSs of these kinases. Furthermore, our studies suggest that ATP-competitive inhibitors can allosterically influence the intracellular binding partners of the JNKs.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Lombard CK,Davis AL,Inukai T,Maly DJdoi
10.1021/acs.biochem.8b00776subject
Has Abstractpub_date
2018-10-09 00:00:00pages
5897-5909issue
40eissn
0006-2960issn
1520-4995journal_volume
57pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:To test for on target toxicity of a new chemical entity, it is important to have comparable binding affinities of the compound in the target proteins from humans and the test species. To evaluate our myeloid cell leukemia-1 (Mcl-1) inhibitors, we tested them against rodent Mcl-1 and found a significant loss of binding...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.8b00626
更新日期：2018-08-14 00:00:00
abstract：:Glu58 is known to participate in phosphodiester transesterification catalyzed by the enzyme RNase T1. For Glu58 RNase T1, an altered mechanism has been proposed in which His40 replaces Glu58 as the base catalyst [Steyaert, J., Hallenga, K., Wyns, L., & Stanssens, P. (1990) Biochemistry 29, 9064-9072]. Glu58Ala Rnase T...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00173a006
更新日期：1994-02-22 00:00:00
abstract：:We have studied the effect of the binding of ribosomal protein S1 and initiation factor IF3 on the accessibility of nucleotide residues 584-1506 in the small subunit of the Escherichia coli ribosome. Protein S1 strongly decreases RNase V1 attack at G1164, in hairpin 40 of the 3' major domain, and weakly decreases DMS ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00112a007
更新日期：1991-12-03 00:00:00
abstract：:Eubacterial peptidyl-tRNA hydrolase (PTH) recycles all N-blocked aminoacyl-tRNA molecules but initiator formyl-methionyl-tRNAfMet, the acceptor helix of which is characterized by a 1-72 mismatch. Positive selection by PTH of noninitiator tRNA molecules with a full 1-72 base pair is abolished, however, upon the removal...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi982657r
更新日期：1999-04-20 00:00:00
abstract：:It now appears that photosynthetic prokaryotes and lower eukaryotes possess higher plant phytochrome-like proteins. In this work, a second phytochrome-like gene was isolated, in addition to the recently identified Cph1 phytochrome, from the Synechocystis sp. PCC 6803, and its gene product was characterized photochemic...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi992831r
更新日期：2000-09-05 00:00:00
abstract：:The association state of the mannitol-specific enzyme II (EIIMtl) has been studied both in the purified form and embedded in the cytoplasmic membrane. Membrane fragments obtained from mannitol-grown Escherichia coli catalyze the phosphoenolpyruvate- (PEP) dependent phosphorylation of both glucose and mannitol; thus th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00319a003
更新日期：1984-11-20 00:00:00
abstract：:The cytological architecture of the synaptonemal complex (SC), a meiosis-specific proteinaceous structure, is evolutionarily conserved among eukaryotes. However, little is known about the biochemical properties of SC components or the mechanisms underlying their roles in meiotic chromosome synapsis and recombination. ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi4005528
更新日期：2013-08-06 00:00:00
abstract：:The effect of ionic strength on the rate constant for electron transfer has been used to determine the magnitude and charge sign of the net electrostatic potential which exists in close proximity to the sites of electron transfer on various c-type cytochromes. The negatively charged ferricyanide ion preferentially rea...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00441a025
更新日期：1989-07-25 00:00:00
abstract：:The distances between the anticodon loops of fluorescent tRNAPhe bound to the E site and to either the A or the P site of poly(U)-programmed Escherichia coli ribosomes were measured by fluorescence energy transfer. Donor and acceptor molecules were wybutine and proflavin, respectively, both located 3' to the anticodon...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00358a002
更新日期：1986-05-20 00:00:00
abstract：:Ribosomal protein E-L30 unfolds reversibly at pH values between 7.0 and 4.5. Unfolding of the protein involves a fast and a slow equilibrium, which depend on the degree of protonation of His19 and His33. Both the fast equilibrium between protonated and deprotonated histidines and the slow equilibrium between folded an...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00391a050
更新日期：1987-08-25 00:00:00
abstract：:The unique structural properties of the ferritin protein cages have provided impetus to focus on the methodical study of these self-assembling nanosystems. Among these proteins, Escherichia coli bacterioferritin (EcBfr), although architecturally very similar to other members of the family, shows structural instability...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi200207w
更新日期：2011-05-17 00:00:00
abstract：:A recombinant form of Rhodobacter sphaeroides phosphoribulokinase (form I; NADH dependent) has been expressed in and purified to homogeneity from Escherichia coli that harbor the prkA gene in the plasmid pKP1565b. Restriction digestion of the phosphoribulokinase-encoding plasmid produces a tractable 450 bp fragment th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00129a022
更新日期：1992-04-14 00:00:00
abstract：:In the ras gene superfamily, codon 12 (-TGGTG-) of the K-ras gene is the most frequently mutated codon in human cancers. Recently, we have found that bulky chemical carcinogens preferentially form DNA adducts at codons 12 and 14 (-CGTAG-) in the K-ras gene in normal human bronchial epithelial (NHBE) cells. Furthermore...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi034631s
更新日期：2003-08-26 00:00:00
abstract：:X-ray solution scattering data from skeletal muscle troponin C and from calmodulin have been measured. Modeling studies based on the crystal structure coordinates for these proteins show discrepancies between the solution data and the crystal structure that indicate that if the size and shape of the globular domains a...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00403a011
更新日期：1988-02-09 00:00:00
abstract：:Melittin is a 26-residue peptide which undergoes high-affinity calcium-dependent binding by calmodulin [Barnette, M.S., Daly, R., & Weiss, B. (1983) Biochem. Pharmacol. 32, 2929; Comte, M., Maulet, Y., & Cox, J.A. (1983) Biochem. J. 209, 269; Anderson, S.R., & Malencik, D.A. (1986) Calcium Cell Funct. 6, 1]. The resul...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00406a021
更新日期：1988-03-22 00:00:00
abstract：:The solution conformation of the ribonuclease barnase has been determined by using 1H nuclear magnetic resonance (NMR) spectroscopy. The 20 structures were calculated by using 853 interproton distance restraints obtained from analyses of two-dimensional nuclear Overhauser spectra, 72 phi and 53 chi 1 torsion angle res...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00099a030
更新日期：1991-09-03 00:00:00
abstract：:The ability of the isomeric quinone metabolites of benzo[a]pyrene, benzo[a]pyrene-6,12-dione, benzo[a]pyrene-1,6-dione, and benzo[a]pyrene-3,6-dione to undergo reversible, univalent oxidation-reduction cycles involving the corresponding benzo[a]pyrenediols and intermediate semiquinone radicals has been characterized. ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00626a035
更新日期：1977-04-05 00:00:00
abstract：:The binding of UDP-N-acetylglucosamine (UDPNAG) to the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) was studied in the absence and presence of the antibiotic fosfomycin by isothermal titration calorimetry. Fosfomycin binds covalently to MurA in the presence of UDPNAG and also in its absence as demonst...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0107041
更新日期：2001-08-21 00:00:00
abstract：:Rhodospirillum rubrum ribulose bisphosphate carboxylase contains two high affinity binding sites for pyridoxal phosphate and two catalytic sites per dimer. However, pyridoxal phosphate binding at only one site is sufficient for inactivation of both catalytic sites. In the presence of 20 mM bicarbonate, 10 mM magnesium...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00600a024
更新日期：1978-04-04 00:00:00
abstract：:It had been reported previously that the beta2 subunit of Escherichia coli tryptophan synthetase [L-serinehydrolyase (adding indole) EC 4.2.1.20] can be cleaved by trypsin into a nearly functional dimeric protein, the monomer of which consists of two large, nonoverlapping, polypeptide fragments. In the present paper, ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00637a012
更新日期：1977-09-06 00:00:00
abstract：:Colicin E3 is a 60 kDa, multidomain protein antibiotic that targets its ribonuclease activity to an essential region of the 16S ribosomal RNA of Escherichia coli. To prevent suicide of the producing cell, synthesis of the toxin is accompanied by the production of a 10 kDa immunity protein (Im3) that binds strongly to ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0273720
更新日期：2003-04-15 00:00:00
abstract：:The protective effect of cyclic stable nitroxide free radicals, having SOD-like activity, against oxidative damage was studied by using Escherichia coli xthA DNA repair-deficient mutant hypersensitive to H2O2. Oxidative damage induced by H2O2 was assayed by monitoring cell survival. The metal chelator 1,10-phenanthrol...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00216a033
更新日期：1991-01-15 00:00:00
abstract：:A core Y61F mutant of the gene 5 single-stranded DNA-binding protein (g5p) of f1 bacterial virus aggregated when expressed from a plasmid, but, after refolding in vitro, it behaved much like wild-type and may be a stability or folding mutant. Circular dichroism (CD) titrations showed the same cooperative polynucleotid...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi972545k
更新日期：1998-05-19 00:00:00
abstract：:Two paramagnetic probes, viz., Mn2+ and Cr3+-ATP, were used to map distances to various loci on carbamoyl-phosphate synthetase by using NMR measurements. The paramagnetic influence of Mn2+ on the 1H of L-glutamate and L-ornithine was measured at 200 and 360 MHz. On the basis of these data, a correlation time for the p...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00277a020
更新日期：1983-04-12 00:00:00
abstract：:Protein folding in vivo takes place in a highly crowded environment. The resulting excluded volume forces are thought to stabilize folded forms of proteins. In agreement, many in vitro studies have shown that the presence of macromolecular crowding agents increases the stability of folded proteins but often by only a ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi500222g
更新日期：2014-04-15 00:00:00
abstract：:We have examined the C cluster in type II CO dehydrogenase (CODH) from Carboxydothermus hydrogenformans using Ni K-edge X-ray absorption near edge spectroscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy. The enzyme was studied under three conditions: "as-isolated" and after treatment with CO or ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi036104e
更新日期：2004-07-20 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：:We identified amino acid residues important for activity of sod2, the Na+/H+ antiporter of Schizosaccharomyces pombe. We mutated all eight His residues of sod2 into Arg. Only His367-->Arg affected function and resulted in complete inability of sod2 to allow growth of S. pombe in LiCl-containing medium. Mutant S. pombe...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9801457
更新日期：1998-06-09 00:00:00
abstract：:The substrate specificities of two incorrectly annotated enzymes belonging to cog3964 from the amidohydrolase superfamily were determined. This group of enzymes are currently misannotated as either dihydroorotases or adenine deaminases. Atu3266 from Agrobacterium tumefaciens C58 and Oant2987 from Ochrobactrum anthropi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi301483z
更新日期：2013-01-08 00:00:00
abstract：:Lactoferrin (Lf) and serum transferrin (Tf) combine high-affinity iron binding with an ability to release this iron at reduced pH. Lf, however, retains iron to significantly lower pH than Tf, giving the two proteins distinct functional roles. In this paper, we compared the iron-release profiles for human Lf, Tf, and t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0001224
更新日期：2000-06-06 00:00:00
