Cytoplasmic tyrosyl-tRNA synthetase (TyrRS) is one of the key enzymes of protein biosynthesis. TyrRSs of pathogenic organisms have gained attention as potential targets for drug development. Identifying structural differences between various TyrRSs will facilitate the development of specific inhibitors for the TyrRSs of pathogenic organisms.
View Article and Find Full Text PDFTyrosyl-tRNA synthetase from Mycobacterium tuberculosis (MtTyrRS) is an enzyme that belongs to class I of aminoacyl-tRNA synthetases, which catalyze the attachment of L-tyrosine to its cognate tRNATyr in the preribosomal step of protein synthesis. MtTyrRS is incapable of cross-recognition and aminoacylation of human cytoplasmic tRNATyr, so this enzyme may be a promising target for development of novel selective inhibitors as putative antituberculosis drugs. As a class I aminoacyl-tRNA synthetase, MtTyrRS contains the HIGH-like and KFGKS catalytic motifs that catalyze amino acid activation with ATP.
View Article and Find Full Text PDFHuman tyrosyl-tRNA synthetase (HsTyrRS) is composed of two structural modules: N-terminal catalytic core and an EMAP II-like C-terminal domain. The structures of these modules are known, but no crystal structure of the full-length HsTyrRS is currently available. An all-atom model of the full-length HsTyrRS was developed in this work.
View Article and Find Full Text PDFEndothelial and monocyte-activating polypeptide II (EMAP II) is a cytokine that plays an important role in inflammation, apoptosis and angiogenesis processes in tumour tissues. Structurally, the EMAP II is a 169 amino acid residues long C-terminal domain (residues 147-312) of auxiliary tRNA binding protein p43. In spite of existence in pdb databank of two X-ray structures there are some important aspects of EMAP II cytokine function which are still not fully understood in detail.
View Article and Find Full Text PDFThe non-catalytic COOH-terminal module formed after proteolytic cleavage of full-length mammalian tyrosyl-tRNA synthetase displays dual function: tRNA binding ability and cytokine activity. With the aim to explore the intramolecular dynamics of C-module in solution we used fluorescence spectroscopy to study conformational changes of isolated protein. We used information from fluorescence spectra and computational model for characterization of a microenvironment of a single tryptophan residue (Trp144).
View Article and Find Full Text PDFMultifunctionality of proteins is among mechanisms accounting for the complexity of interactome networks in higher eukaryotes. During oncogenesis and other pathologic conditions many proteins perform additional functions without changes in three dimensional structures. One family of these moonlighting proteins is represented by enzymes and cofactors of aminoacylation reactions, by means of which tRNAs are attached to their cognate amino acids.
View Article and Find Full Text PDFHIV-1 protease is most active under weakly acidic conditions (pH 3.5-6.5), when the catalytic Asp25 and Asp25' residues share 1 proton.
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