Identification of Two Non-Peptidergic Small Molecule Inhibitors of CBX2 Binding to K27 Trimethylated Oligonucleosomes.

The dysregulation of the PRC1/2 complex plays a key role in lineage plasticity in prostate cancer and may be required to maintain neuroendocrine phenotype. [1] CBX2, a key component of the canonical PRC1 complex, is an epigenetic reader, recognizing trimethylated lysine on histone 3 (H3K27me3) [2] and is overexpressed in metastatic neuroendocrine prostate cancer. [3,4] We implemented a screening strategy using nucleosome substrates to identify inhibitors of CBX2 binding to chromatin.

Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif.

Atypical protein kinases C (aPKCs) play critical roles in signaling pathways that control cell growth, differentiation and survival. Therefore, they constitute attractive targets for the development of novel therapeutics against cancer. The crystal structure of the catalytic domain of atypical PKCiota in complex with the bis(indolyl)maleimide inhibitor BIM1 has been determined at 3.

Cloning, sequencing, crystallization and X-ray structure of glutathione S-transferase-III from Zea mays var. mutin: a leading enzyme in detoxification of maize herbicides.

Glutathione S-transferases (GSTs) are enzymes that inactivate toxic compounds by conjugation with glutathione and are involved in resistance towards drugs, antibiotics, insecticides and herbicides. Their ability to confer herbicide tolerance in plants provides a tool to control weeds in a wide variety of agronomic crops. GST-III was prepared from Zea mays var.

Crystal structure of herbicide-detoxifying maize glutathione S-transferase-I in complex with lactoylglutathione: evidence for an induced-fit mechanism.

Glutathione S-transferases (GSTs) -I and -III are involved in herbicide metabolism in maize and have been intensively studied. Starting with plant tissue from Zea mays var. mutin recombinant GST-I was prepared by heterologous expression in Escherichia coli.

Bioincorporation of telluromethionine into proteins: a promising new approach for X-ray structure analysis of proteins.

A simple and efficient method for the specific and quantitative replacement of the naturally occurring amino acid methionine by its isosteric analogue telluromethionine in the expression of recombinant proteins has been developed. The method requires a controlable and competitive expression system like the bacteriophage T7 polymerase/promoter in a methionine-auxotrophic host. Using methionine-auxotrophic Escherichia coli strains, incorporation of telluromethionine at high yields has been achieved for human recombinant annexin V, human mitochondrial transamidase, Arabidopsis glutathione-S-transferase and the N-terminal domain of Salmonella tailspike adhesion protein as confirmed by amino acid, mass-spectrometric and X-ray analyses.