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Rybchenko V. S. Panina A. A. Novoseletsky N. V. Balabashin D. S. Yakimov S. A. Solopova O. N. Sveshnikov P. G. Aliev T. K. Dolgikh D. A. Kirpichnikov M. P. 《Russian Journal of Bioorganic Chemistry》2020,46(5):778-786
Russian Journal of Bioorganic Chemistry - Humanization of antibodies for the development of novel therapeutic agents with low immunogenicity remains a topical problem in modern science. In the... 相似文献
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Larina M. V. Finashutina Y. P. Lyzhko N. A. Misyurin V. A. Novoseletsky V. N. Dolgikh D. A. Solopova O. N. Moysenovich A. M. Balabashin D. S. Aliev T. K. Misyurin A. V. Kirpichnikov M. P. 《Russian Journal of Bioorganic Chemistry》2022,48(2):360-371
Russian Journal of Bioorganic Chemistry - The PRAME antigen, which is a significant target for monoclonal antibodies, is a tumor-specific marker that is active at all stages of tumor cell... 相似文献
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A study of bacterial surface oligosaccharides were investigated among
different strains of Neisseria gonorrhoeae to correlate structural features
essential for binding to the MAb 2C7. This epitope is widely expressed and
conserved in gonococcal isolates, characteristics essential to an effective
candidate vaccine antigen. Sample lipooligosaccharides (LOS), was prepared
by a modification of the hot phenol-water method from which de-O-acetylated
LOS and oligosaccharide (OS) components were analyzed by ES-MS-CID-MS and
ES-MSnin a triple quadrupole and an ion trap mass spectrometer,
respectively. Previously documented natural heterogeneity was apparent from
both LOS and OS preparations which was admixed with fragments induced by
hydrazine and mild acid treatment. Natural heterogeneity was limited to
phosphorylation and antenni extensions to the alpha-chain. Mild acid
hydrolysis to release OS also hydrolyzed the beta(1-->6) glycosidic
linkage of lipid A. OS structures were determined by collisional and
resonance excitation combined with MS and multistep MSn which provided
sequence information from both neutral loss, and nonreducing terminal
fragments. A comparison of OS structures, with earlier knowledge of MAb
binding, enzyme treatment, and partial acid hydrolysis indicates a generic
overlapping domain for 2C7 binding. Reoccurring structural features include
a Hepalpha(1-->3)Hepbeta(1-->5)KDO trisaccharide core branched on the
nonreducing terminus (Hep-2) with an alpha(1-->2) linked GlcNAc
(gamma-chain), and an alpha-linked lactose (beta-chain) residue. From the
central heptose (Hep-1), a beta(1-->4) linked lactose (alpha-chain),
moiety is required although extensions to this residue appear unnecessary.
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A. D. Volyntseva V. N. Novoseletsky K. V. Shaitan A. V. Feofanov 《Moscow University Biological Sciences Bulletin》2017,72(1):25-29
The Kv1.3 voltage-gated potassium channel is involved in a number of processes in excitable and nonexcitable cells: maintenance of resting membrane potential, signal transduction, apoptosis, regulation of cell volume, activation and proliferation of white blood cells. Blocking this channel is an effective approach for the treatment of autoimmune, oncological, chronic inflammatory, and metabolic diseases. The most prospective blockers of Kv1.3 are toxins isolated from the venom of scorpions. Knowledge of the molecular aspects of binding of peptide blockers with the channel is an important condition for the creation of highly effective and selective ligands. In the present work, a complex of hybrid channel KcsA-Kv1.3 with agitoxin 2 was built using homology modeling and molecular dynamics simulation. Analysis of formed contacts allowed us to reveal a complete pattern of interactions and to identify key residues that are responsible for the toxin binding affinity. Results of computational experiment are consistent with the experimental data and important for drug development. 相似文献
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Effect of self-association on the structural organization of partially folded proteins: inactivated actin 总被引:1,自引:0,他引:1 下载免费PDF全文
IM Kuznetsova AG Biktashev SY Khaitlina KS Vassilenko KK Turoverov VN Uversky 《Biophysical journal》1999,77(5):2788-2800
The propensity to associate or aggregate is one of the characteristic properties of many nonnative proteins. The aggregation of proteins is responsible for a number of human diseases and is a significant problem in biotechnology. Despite this, little is currently known about the effect of self-association on the structural properties and conformational stability of partially folded protein molecules. G-actin is shown to form equilibrium unfolding intermediate in the vicinity of 1.5 M guanidinium chloride (GdmCl). Refolding from the GdmCl unfolded state is terminated at the stage of formation of the same intermediate state. An analogous form, known as inactivated actin, can be obtained by heat treatment, or at moderate urea concentration, or by the release of Ca(2+). In all cases actin forms specific associates comprising partially folded protein molecules. The structural properties and conformational stability of inactivated actin were studied over a wide range of protein concentrations, and it was established that the process of self-association is rather specific. We have also shown that inactivated actin, being denatured, is characterized by a relatively rigid microenvironment of aromatic residues and exhibits a considerable limitation in the internal mobility of tryptophans. This means that specific self-association can play an important structure-forming role for the partially folded protein molecules. 相似文献
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Petrovskaya LE Shingarova LN Kryukova EA Boldyreva EF Yakimov SA Guryanova SV Novoseletsky VN Dolgikh DA Kirpichnikov MP 《Biochemistry. Biokhimii?a》2012,77(1):62-70
Tumor necrosis factor (TNF) plays a key role in the pathogenesis of various diseases. To study the possibility of constructing
TNF-binding proteins by grafting hypervariable regions of immunoglobulins (CDR), we have replaced amino acid sequences of
loops from the tenth type III domain of human fibronectin (10Fn3) by amino acid sequences of CDR from the light and heavy chains of the anti-TNF antibody F10. The assessment of TNF-binding
properties of the resulting proteins by ELISA has revealed the highest activity of Hd3 containing sequences CDR-H1 and CDR-H2
of the antibody F10 and of Hd2 containing sequences CDR-H1 and CDR-H3. The proteins constructed by us on the fibronectin domain
scaffold specifically bound TNF during Western blotting and also weakened its cytotoxic effect on L929 line cells. The highest
neutralizing activity was demonstrated by the proteins Hd2 and Hd3, which induced, respectively, 10- and 50-fold increase
in the EC50 of TNF. 相似文献
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V. N. Novoseletsky A. D. Volyntseva K. V. Shaitan O. S. Sokolova 《Moscow University Biological Sciences Bulletin》2017,72(2):69-73
A voltage-gated potassium channel Kv10.2 is expressed in the nervous system, but its functions and involvement in the development of human disease remain poorly understood. Mutant forms of the Kv10.2 channel were found in patients with epileptic encephalopathy and autism. Molecular modeling of the channel spatial structure is an important tool for gaining knowledge about the molecular aspects of the channel functioning and mechanisms responsible for pathogenesis. In the present work, molecular modeling of the helical fragment of the human Kv10.2 (hEAG2) C-terminal domain in dimeric, trimeric, and tetrameric forms was performed. The stability of all forms was confirmed by molecular dynamics simulation. Contacts and interactions, stabilizing the structure, were identified. 相似文献
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