Search results for " Dimerization"
showing 10 items of 15 documents
Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes
2018
Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these unicellular eukaryotic parasites differs from the human host and their enzymes thus constitute promising drug targets. Tryparedoxin (Tpx) from Trypanosoma brucei is the essential oxidoreductase in the parasite's hydroperoxide-clearance cascade. In vitro and in vivo functional assays show that a small, selective inhibitor efficiently inhibits Tpx. With X-ray crystallography, SAXS, analytical SEC, SEC-MALS, MD simulations, ITC, and NMR spectroscopy, we show how covalent binding of this monofunctional inhibitor leads to Tpx dimerization. Intra- and intermolecular inhibitor-inhibitor, pro…
Ein neuer Syntheseweg zu Offenkettigen und cyclischen Oligoetherketonen
1998
A Novel Synthetic Route to Open-Chained and Cyclic Oligoetherketones Oligoetherketones of the structure 2a,b can be generated by repetitive insertion reactions of terminal biscarbenoids 4a,b, into the OH bonds of diols like 5. The formation of the corresponding ring systems 7a and the involved carbene dimerization leading to 8b are processes which compete with the linear polyinsertion. A related one-component reaction can be performed with ω-hydroxy-1-diazo-2-alkanones (13a–c 14a–c).
The role of hydrophobic matching on transmembrane helix packing in cells
2017
Folding and packing of membrane proteins are highly influenced by the lipidic component of the membrane. Here, we explore how the hydrophobic mismatch (the difference between the hydrophobic span of a transmembrane protein region and the hydrophobic thickness of the lipid membrane around the protein) influences transmembrane helix packing in a cellular environment. Using a ToxRED assay in Escherichia coli and a Bimolecular Fluorescent Complementation approach in human-derived cells complemented by atomistic molecular dynamics simulations we analyzed the dimerization of Glycophorin A derived transmembrane segments. We concluded that, biological membranes can accommodate transmembrane homo-di…
Enhancement of the FGFR1 signaling in the FGFR1-5-HT1A heteroreceptor complex in midbrain raphe 5-HT neuron systems. Relevance for neuroplasticity an…
2015
New findings show existence of FGFR1-5-HT1A heteroreceptor complexes in 5-HT nerve cells of the dorsal and median raphe nuclei of the rat midbrain and hippocampus. Synergistic receptor-receptor interactions in these receptor complexes indicated their enhancing role in hippocampal plasticity. The existence of FGFR1-5-HT1A heteroreceptor complexes also in midbrain raphe 5-HT nerve cells open up the possibility that antidepressant drugs by increasing extracellular 5-HT levels can cause an activation of the FGF-2/FGFR1 mechanism in these nerve cells as well. Therefore, the agonist modulation of the FGFR1-5-HT1A heteroreceptor complexes and their specific role is now determined in rat medullary …
Insight into the mechanism of diazocompounds transformation catalyzed by hetero cuboidal clusters [Mo3CuQ4(MeBPE)3X4]+, (Q=S, Se; X=Cl, Br): The cata…
2008
Abstract Two enantiomerically pure trinuclear compounds of formula (P)-[Mo3S4{(R,R)-Me–BPE}3Br3]Br and (P)-[Mo3Se4{(R,R)-Me–BPE}3Cl3]Cl, (P)-1b.Br and (P)-1c.Cl, respectively, have been synthesized in a good yield and a stereospecific manner by excision of polymeric [Mo3Q7X4]n (Q = S or Se, X = Cl or Br) phases with (R,R)-Me–BPE{1,2-bis[(2R,5R)-2,5-(dimethylphospholan-1-yl)]ethane}. They have been transformed into chiral hetereo cuboidal compounds [Mo3S4{(R,R)-Me–BPE}3Br3]PF6, (P)-2b.PF6, and [Mo3Se4{(R,R)-Me–BPE}3Cl3]PF6, (P)-2c.PF6, by reaction with copper salts. All these compounds have been characterized by 31P NMR, IR, UV–Vis, mass spectrometry, elemental analysis, and chiral dichroism…
Heterodimerization of Two Pathological Mutants Enhances the Activity of Human Phosphomannomutase2
2015
The most frequent disorder of glycosylation is due to mutations in the gene encoding phosphomannomutase2 (PMM2-CDG). For this disease, which is autosomal and recessive, there is no cure at present. Most patients are composite heterozygous and carry one allele encoding an inactive mutant, R141H, and one encoding a hypomorphic mutant. Phosphomannomutase2 is a dimer. We reproduced composite heterozygosity in vitro by mixing R141H either with the wild type protein or the most common hypomorphic mutant F119L and compared the quaternary structure, the activity and the stability of the heterodimeric enzymes. We demonstrated that the activity of R141H/F119L heterodimers in vitro, which reproduces t…
Mcl-1 and Bok transmembrane domains : Unexpected players in the modulation of apoptosis
2020
The Bcl-2 protein family comprises both proand antiapoptotic members that control the permeabilization of the mitochondrial outer membrane, a crucial step in the modulation of apoptosis. Recent research has demonstrated that the carboxyl-terminal transmembrane domain (TMD) of some Bcl-2 protein family mem-bers can modulate apoptosis; however, the transmembrane interactome of the antiapoptotic protein Mcl-1 remains largely unexplored. Here, we demonstrate that the Mcl-1 TMD forms homooligomers in the mitochondrial membrane, competes with full-length Mcl-1 protein with regards to its antiapoptotic function, and induces cell death in a Bok-dependent manner. While the Bok TMD oligomers locate p…
Novel mixed-valence Cu compounds formed by Cu(II) dimers with double oximato bridges: in situ formation of anionic layer [Cu2(SCN)3]n(n-).
2013
Two new N3O donor ketoxime Schiff bases (HL(1) and HL(2)) have been synthesized by condensing N,N-dimethylethylenediamine with diacetylmonoxime and benzilmonoxime, respectively in a 1:1 ratio. Reaction of Cu(ClO4)2·6H2O with HL(1) resulted in a discrete oximato-bridged dinuclear Cu(II) complex [Cu2(L(1))2(H2O)2](ClO4)2 (1). The same reaction in presence of NaSCN affords the complex {[Cu(II)2(L(1))2][Cu(I)4(μ(1,3)-SCN)4(μ(1,1,3)-SCN)2]}n (2), where partial Cu(II)→Cu(I) reduction is observed. In 2, arrays of [Cu(II)2(L(1))2](2+) cationic units are inserted in between 2D {[Cu(I)4(SCN)6](2-)}n layers and connected via μ(1,1,3)-SCN(-) links, thus forming a 3D network. On the other hand, reaction…
The abrogation of the HOXB7/PBX2 complex induces apoptosis in melanoma through the miR-221&222-c-FOS pathway.
2013
Cutaneous melanoma is the fastest increasing cancer worldwide. Although several molecular abnormalities have been associated with melanoma progression, the underlying mechanisms are still largely unknown and few targeted therapies are under evaluation. Here we show that the HOXB7/PBX2 dimer acts as a positive transcriptional regulator of the oncogenic microRNA-221 and -222. In addition, demonstrating c-FOS as a direct target of miR-221&222, we identify a HOXB7/PBX2→miR-221&222 →c-FOS regulatory link, whereby the abrogation of functional HOXB7/PBX2 dimers leads to reduced miR-221&222 transcription and elevated c-FOS expression with consequent cell death. Taking advantage of the treatment wit…
Comparative chemistry of 18-electron Mo(II) and 17-electron Mo(III) compounds containing only carbon-based ligands
1998
International audience; The chemical reactivity of various kinetically stable isomers of compound CpMo(η3-C3H5)(η4-C4H6), 1, and its oxidation product [1]+, as well as the bis-allyl Mo(III) complex CpMo(η3-C3H5)2, 2, and the bis-diene Mo(II) complex [CpMo(η4-C4H6)2]+, 3, is reviewed. The inertness toward isomerization processes of the allyl and butadiene ligands in the Mo(II) complexes has allowed a study of the relative reactivity toward both electrophilic and nucleophilic addition processes as a function of coordination mode. The dependence of various reaction pathways on the metal oxidation state has also been investigated. Of particular interest is the discovery that the electronically …