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Distribution by Scientific Domains

Chemistry	80%

Selected Abstracts

The Janus-faced atracotoxins are specific blockers of invertebrate KCa channels

FEBS JOURNAL, Issue 16 2008
Simon J. Gunning
The Janus-faced atracotoxins are a unique family of excitatory peptide toxins that contain a rare vicinal disulfide bridge. Although lethal to a wide range of invertebrates, their molecular target has remained enigmatic for almost a decade. We demonstrate here that these toxins are selective, high-affinity blockers of invertebrate Ca2+ -activated K+ (KCa) channels. Janus-faced atracotoxin (J-ACTX)-Hv1c, the prototypic member of this toxin family, selectively blocked KCa channels in cockroach unpaired dorsal median neurons with an IC50 of 2 nm, but it did not significantly affect a wide range of other voltage-activated K+, Ca2+ or Na+ channel subtypes. J-ACTX-Hv1c blocked heterologously expressed cockroach large-conductance Ca2+ -activated K+ (pSlo) channels without a significant shift in the voltage dependence of activation. However, the block was voltage-dependent, indicating that the toxin probably acts as a pore blocker rather than a gating modifier. The molecular basis of the insect selectivity of J-ACTX-Hv1c was established by its failure to significantly inhibit mouse mSlo currents (IC50 , 10 ,m) and its lack of activity on rat dorsal root ganglion neuron KCa channel currents. This study establishes the Janus-faced atracotoxins as valuable tools for the study of invertebrate KCa channels and suggests that KCa channels might be potential insecticide targets. [source]

Caspase activation, inhibition, and reactivation: A mechanistic view

PROTEIN SCIENCE, Issue 8 2004
Yigong Shi
Abstract Caspases, a unique family of cysteine proteases, execute programmed cell death (apoptosis). Caspases exist as inactive zymogens in cells and undergo a cascade of catalytic activation at the onset of apoptosis. The activated caspases are subject to inhibition by the inhibitor-of-apoptosis (IAP) family of proteins. This inhibition can be effectively removed by diverse proteins that share an IAP-binding tetrapeptide motif. Recent structural and biochemical studies have revealed the underlying molecular mechanisms for these processes in mammals and in Drosophila. This paper reviews these latest advances. [source]

Passively acquired anti-SSA/Ro antibodies are required for congenital heart block following ovodonation but maternal genes are not

ARTHRITIS & RHEUMATISM, Issue 10 2010
Antonio Brucato
Anti-SSA/Ro antibodies are necessary but not sufficient to provoke autoimmune-associated congenital heart block (CHB). Genetic factors are likely contributory. Accordingly, HLA-related candidates and single-nucleotide polymorphisms in the promoter region of tumor necrosis factor , and codon 10 in transforming growth factor ,1 (TGF,1) were evaluated in a unique family: the surrogate mother (anti-SSA/Ro positive), the biologic father, and the CHB-affected child (product of ovodonation). There was an HLA mismatch between the affected child and the surrogate mother. However, both the biologic and the surrogate mothers shared DQ2 and the profibrosing leucine polymorphism at codon 10 of TGF,. In conclusion, we observed that CHB can develop in a genetically unrelated child exposed in utero to anti-SSA/Ro antibodies. Testing for anti-SSA/Ro antibodies might be considered in women undergoing artificial fertilization. It is possible that there is no direct association of maternal genes beyond a contributory role in generating the autoantibody. [source]

Isolation, purification and preliminary X-ray characterization of Cpn60-2 (65,kDa heat-shock protein) from Mycobacterium tuberculosis

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 9 2002
Noam Adir
Cpn60-2 is a member of a unique family of putative molecular chaperones homologous to GroEL (Cpn60) but of unknown function and found only in Mycobacterium tuberculosis and closely related species. Cpn60-2 has mainly been studied for its strong immunogenity. Here, the purification, crystallization and preliminary crystallographic analysis of M. tuberculosis Cpn60-2 are reported. The crystals belong to space group P2, with unit-cell parameters a = 57, b = 115.5, c = 81.5,Å, , = 95.5°, and contain a dimer in the asymmetric unit. The crystals diffract to 4.0,Å using a Cu rotating-anode X-ray generator. [source]

The Cyclotide Fingerprint in Oldenlandia affinis: Elucidation of Chemically Modified, Linear and Novel Macrocyclic Peptides

CHEMBIOCHEM, Issue 9 2007
Manuel Rey R. Plan Dr.
Abstract The complete suite of cyclotides present in Oldenlandia affinis (Rubiaceae), the plant that was originally found to contain this unique family of circular proteins, has been characterised. This study expands the number of known cyclotides in this plant to 17, of which nine new sequences (kalata B9,B17) were characterised in this work. In addition, five derivatives that contain oxidation products of the conserved tryptophan were identified, and it was shown that the formation of these derivatives is catalysed by exposure to sunlight. Furthermore, we describe two "linear" cyclotide analogues. These acyclic peptides have three intact disulfide bonds, and their N and C termini coincide with the hypothesised cleavage sites from the precursor protein. This work increases our knowledge about the sequence variation that is accommodated by the cyclic cystine knot scaffold, confirms its applicability as a template for drug design, and also shows the first natural degradation pathways for cyclotides. These pathways have important implications for the persistence and environmental fate of the cyclotides if used as crop-protection agents. [source]