Allosteric inhibition
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In continuation of our interest in identifying new α-glucosidase inhibitors with potential to become antidiabetic drugs, this work focuses on the study of 4-(dimethylaminoalkyl)piperazine-1-carbodithioate derivatives as α-glucosidase inhibitors. The eight heterocyclic piperazine-dithiocarbamate complexes studied in this work contain a variety of substitutions on their benzene ring exhibiting potent, noncompetitive inhibition of α-glucosidase.
9p lyhuyenthu 31-01-2023 9 2 Download
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CRISPR-Cas9 has been developed as a therapeutic agent for various infectious and genetic diseases. In many clinically relevant applications, constitutively active CRISPR-Cas9 is delivered into human cells without a temporal control system. Excessive and prolonged expression of CRISPR-Cas9 can lead to elevated off-target cleavage.
15p viarchimedes 26-01-2022 7 0 Download
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Philadelphia positive leukemias are characterized by the presence of Bcr-Abl fusion protein which exhibits an abnormal kinase activity. Selective Abl kinase inhibitors have been successfully established for the treatment of Ph (+) leukemias.
10p vijisoo2711 30-09-2020 14 2 Download
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NS4A is a non-structural multi-tasking small peptide that is essential for HCV maturation and replication. The central odd-numbered hydrophobic residues of NS4A (Val-23‘ to Leu-31‘)i are essential for activating NS3 upon NS3/4A protease complex formation. This study aims to design new specific allosteric NS3/4A protease inhibitors by mutating Val-23‘, Ile-25‘, and Ile-29‘ into bulkier amino acids. Pep-15, a synthetic peptide, showed higher binding affinity towards HCV-NS3 subtype-4 than native NS4A. The Kd of Pep-15 (80.0 ± 8.0 nM) was twice as high as that of native NS4A (169 ± 37 nM).
9p partimesinhvien 08-05-2020 15 1 Download
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Nitric oxide (NO), the principal endogenous ligand for soluble guanylate cyclase (sGC), stimulates that enzyme and accumulation of intracellular cGMP, which mediates many of the (patho) physiological effects of NO. Previous studies demonstrated that 2-substituted adenine nucleotides, including 2-methylthioATP (2MeSATP) and 2-chloroATP (2ClATP), allosterically inhibit guanylate cyclase C, the membrane-bound receptor for the Escherichia coli heatstable enterotoxin in the intestine. The present study examined the effects of 2-substituted adenine nucleotides on crude and purified sGC. ...
8p research12 01-06-2013 35 3 Download
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This work proposes a model of the metabolic branch-point between the methionine and threonine biosynthesis path-ways inArabidopsis thalianawhich involves kinetic compe-tition for phosphohomoserine between the allosteric enzyme threonine synthase and the two-substrate enzyme cysta-thionine c-synthase. Threonine synthase is activated by S-adenosylmethionine and inhibited by AMP. Cystathio-ninec-synthase condenses phosphohomoserine to cysteine via a ping-pong mechanism.
13p fptmusic 12-04-2013 35 2 Download
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Aspartate transcarbamylase from the hyperthermophilic archaeon Pyrococcus abyssi Insights into cooperative and allosteric mechanisms Sigrid Van Boxstael1, Dominique Maes2,3 and Raymond Cunin1 1 Erfelijkheidsleer en Microbiologie, Vrije Universiteit Brussel, Belgium 2 Ultrastructuur, Vrije Universiteit Brussel, Belgium 3 Vlaams Interuniversitair Instituut voor Biotechnologie, Belgium Keywords allostery; aspartate transcarbamylase; cooperativity; inhibition by analogues; Pyrococcus abyssi Correspondence R.
14p awards 06-04-2013 39 2 Download
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Theuppgene, encoding uracil phosphoribosyltransferase (UPRTase) from the thermoacidophilic archaeon Sulfolobus solfataricus, was cloned and expressed inEscherichia coli. The enzyme was purified to homogeneity. It behaved as a tetramer in solution and showed optimal activity at pH 5.5 when assayed at 60C. Enzyme activity was strongly stimulated by GTP and inhibited by CTP.
14p awards 06-04-2013 21 3 Download
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Temperature effects on the kinetic properties of phosphofructokinase (PFK) purified from skeletal muscle of the golden-mantled ground squirrel, Spermophilus lateralis, were examined at 37 C and 5C, values character-istic of body temperatures in euthermia vs. hibernation. The enzyme showed reduced sensitivity to all activators at 5C, theKa values for AMP, ADP, NH4 + and F2,6P2 were 3–11-fold higher at 5C than at 37C. Inhibition by citrate was not affected whereas phosphoenolpyruvate, ATP and urea became more potent inhibitors at low temperature. ...
0p awards 05-04-2013 39 1 Download
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Malonyl-CoA, a potent inhibitor of carnitine pamitoyl transferase-I (CPT-I), plays a pivotal role in fuel selection in cardiac muscle. Malonyl-CoA decarboxylase (MCD) cata-lyzes the degradation of malonyl-CoA, removes a potent allosteric inhibition on CPT-I and thereby increases fatty acid oxidation in the heart. Although MCDhas several Ser/ Thr phosphorylation sites, whether it is regulated by AMP-activated protein kinase (AMPK) has been controversial. We therefore overexpressed MCD(Ad.MCD) and consti-tutively active AMPK (Ad.
10p dell39 03-04-2013 36 2 Download
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Plant monofunctional aspartate kinase is unique among all aspartate kinases, showing synergistic inhibition by lysine and S-adenosyl-l-methionine (SAM). The Arabidopsisgenome contains three genes for monofunctional aspartate kinases. We show that aspartate kinase 2 and aspartate kinase 3 are inhibited only by lysine, and that aspartate kinase 1 is inhibited in a synergistic manner by lysine and SAM.
13p inspiron33 23-03-2013 37 2 Download