生物化学技术

Post-translational modification of proteins, such as phosphorylation, ubiquitination, and SUMO modification, is an important means of regulating a variety of cellular activities. SUMOs (Small Ubiquitin related Modifiers) are covalently conjugated to lysine residues of ma ...

SUMO conjugation to protein substrates requires the concerted action of a dedicated E2 ubiquitin conjugation enzyme (Ubc9) and associated E3 ligases. Although Ubc9 can directly recognize and modify substrate lysine residues that occur within a consensus site for SUMO modificatio ...

Post-translational modification by SUMO is an important mechanism to regulate transcription. Sumoyla-tion has diverse effects on substrate activity, but in most cases reported to date sumoylation of transcription factors correlated with transcriptional repression. Here ...

Sumoylation of proteins in vitro has evolved as an indispensable tool for the functional analysis of this post-translational modification. In this article we present detailed protocols for bacterial production of mammalian proteins necessary to perform in vitro sumoylation rea ...

The bottleneck in studying protein sumoylation—the conjugation of the small ubiquitin-like modifier (SUMO)—is the detection of the low level of in vivo sumoylated proteins. The Ubc9 fusion-directed sumoylation (UFDS) system strongly enhances the in vivo sumoylation of a substrate ...

Covalent modification of proteins by small ubiquitin-like modifier (SUMO) regulates diverse cellular processes. While many SUMO substrates are identified through individual efforts, affinity-based approaches followed by mass spectrometry are also used to identify in vivo ...

The covalent modification of cellular factors by the small ubiquitin-like modifier (SUMO) has emerged as a key regulatory pathway for many biological processes. One recent advance in the field of SUMO modification that has provided important insights into SUMO-mediated regulatory n ...

The identification of target proteins for small ubiquitin-like modifiers (SUMOs) is a critical step towards a detailed understanding of the cellular functions of SUMOs. Substrate protein identification for SUMOs is hampered by the low abundance of SUMO targets, the finding that only a sm ...

Post-translational modification by SUMO is now recognized as an important regulatory method employed by the cell to reversibly modulate the activity, stability, or localization of intracellular proteins. A dedicated enzymatic machinery is involved in the processing, attachm ...

Chemogenomics knowledge-based drug discovery approaches aim to extract the knowledge gained from one target and to apply it for the discovery of ligands and hopefully drugs of a new target which is related to the parent target by homology or conserved molecular recognition. Herein, we demon ...

Several database systems have been developed to provide valuable information from the bench chemist to biologist, medical practitioner to pharmaceutical scientist in a structured format. The advent of information technology and computational power enhanced the ability to acc ...

During molecular recognition of proteins in biological systems, helices, reverse turns, and β-sheets are dominant motifs. Often there are therapeutic reasons for blocking such recognition sites, and significant progress has been made by medicinal chemists in the design and synthes ...

Cofactors are organic molecules, most of them originating from vitamins, that bind to enzymes making them able to catalyze defined reactions. A cofactor-based chemogenomics approach exploits the presence of a cofactor-binding domain to develop compound scaffolds tailored to mim ...

Purines are critical cofactors in the enzymatic reactions that create and maintain living organisms. In humans, there are approximately 3,266 proteins that utilize purine cofactors and these proteins constitute the so-called purinome. The human purinome encompasses a wide-rang ...

Chemogenomics is a modern approach to analysis of the biological effect of a wide array of small molecule compounds on a large set of homologous receptors or other macromolecular drug targets. However, the relative productivity of the method and the extremely high-cost procedure jointly f ...

The sequencing of genomes gave access to the complete set of building blocks for organisms of various species. A plethora of “-omics”-technologies has been developed to investigate the dynamic interactions of the building blocks in order to understand the functioning of living organism ...

Phenotypic chemogenomics studies require screening strategies that account for the complex nature of the experimental system. Unknown mechanism of action and high frequency of false positives and false negatives necessitate iterative experiments based on hypotheses form ...

Analysis of the three-dimensional structures of protein ligand complexes provides valuable insight into both the common interaction patterns within a target family and the discriminating features between the different members of a target family. Knowledge of the common interac ...

Biological metabolites, substrates, cofactors, chemical probes, and drugs bind to flexible pockets in multiple biological macromolecules to exert their biological effect. The rapid growth of the structural databases and sequence data, including SNPs and disease-related gen ...

We describe an integrated system that brings together predictive chemical analyses based on compound structure, knowledge bases of chemogenomics data associating compounds to biological, pharmacological and toxicological properties, and a systems biology functional d ...