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A M Andrianov

Publications and source records attributed to A M Andrianov.

At least 19 recordsLinked to original sources
PubMed2006

Determination of structurally conservative amino acids of the HIV-1 protein gp120 V3 loop as promising targets for drug design by protein engineering approaches.

Based on the published NMR spectroscopy data, three-dimensional structures of the HIV-1 gp120 protein V3 loop were obtained by computer modeling in the viral strains HIV-Haiti and HIV-MN. In both cases, the secondary structure elements and conformations of irregular stretches were determined for the fragment representing the principal antigenic determinant of the virus, as well as determinants of the cellular tropism and syncytium formation. Notwithstanding the high variability of the amino acid sequence of gp120 protein, more than 50% of the V3 loop residues retained their conformations in the different HIV-1 virions. The combined analysis of the findings and the literature data on the biological activity of the individual residues of the HIV-1 V3 loop resulted in identification of its structurally conservative amino acids, which seem to be promising targets for antiviral drug design by protein engineering approaches.

Amino Acid Sequence↗
PubMed2006

[Conformation of the HIV-1 gp120 V3 loop. Structure functional analysis of the HIV-Haiti viral strain].

The structural model describing the conformational preferences of the HIV-Haiti gp120 V3 loop in geometric space of dihedral angles was generated in terms of NMR spectroscopy data using the methods of computer modeling. The elements of secondary structure anti conformations of irregular stretches were deciphered for the fragment making the virus principal neutralizing determinant as well as the determinants of cell tropism and syncytium formation. The structurally conserved amino acids of the HIV-1 V3 loop, that may present the forward-looking targets for AIDS drug design, were identified based on the combined analysis of the results obtained with those derived previously. In particular, it was demonstrated that the register of these amino acids comprises Asn-25 critical for virus binding with primary cell receptor CD4 as well as Arg-3 critical for utilization of CCR5 coreceptor and heparan sulfate proteoglycan syndecans. The results obtained are discussed in conjunction with the literature data on the biological activity of individual amino acid residues of the HIV-1 gpl20 V3 loop.

Amino Acid Sequence↗
PubMed2005

Conformational preferences of the HIV-1 principal neutralizing determinant.

The model describing the conformational properties of the HIV-1 principal neutralizing determinant in the geometric space of dihedrals was generated in terms of NMR spectroscopy data published in literature. To gain an object in view, the following successive steps were put into effect: (i) the NMR-based local structures for the HIV(MN) V3 loop were determined in water and in a mixed water/trifluoroethanol (TFE) solvent (7:3), (ii) in either case, the conformations of its irregular segments were analyzed and the secondary structure elements identified, (iii) to appreciate the degree of conformational mobility of the stretch of interest, the simulated structures were compared with each other, (iv) to detect the amino acids retaining their conformations inside the diverse HIV-1 isolates, the structures computed were collated with the one derived previously for the V3 loop from Thailand isolate, and (v) as a matter of record, the structurally rigid residues, that may present the forward-looking targets for AIDS drug researches, were revealed. Summing up the principal results arising from these studies, the following conclusions were drawn: I. The HIV(MN) V3 loop offers the highly mobile fragment of gp120 sensitive to its environment whose changes trigger the large-scale structural reforms, bringing in substantial altering the secondary structure of this functionally important site of the virus envelope. II. In water, it exhibits extended site 1-14 separated by double beta-turn 15-20 with unordered region 21-35. III. Adding the TFE gives rise to destruction of the regular structure in the V3 loop N-terminal, stimulates the formation of 3(10)-helix in site 24-31, and affects also its central region 20-25 forming the HIV-1 immunogenic crown. IV. Regardless of statistically significant differences between local structures of the HIV(MN) V3 loop in water and in water/TFE solution, over one-third of residues keeps their conformational states; the register of these amino acids comprises Asn-25 critical for virus binding with primary cell receptor CD4 as well as Arg-3 critical for utilization of CCR5 coreceptor. V. There are no conserved structural motifs within the V3 loops from Minnesota and Thailand HIV-1 strains. However, perceptible portion of amino acids (more than 35%), including those appearing in the functionally important regions of gp120, holds the values of dihedral angles in which case. The implications are discussed in conjunction with the data on the experimental observations for the HIV-1 principal neutralizing determinant.

Amino Acid Sequence↗
PubMed1999

Global and local structural properties of the principal neutralizing determinant of the HIV-1 envelope protein gp120.

The model of spatial structure for the principal neutralizing determinant (PND) of the HIV-1 envelope protein gp120 is proposed in terms of two-dimensional nuclear Overhauser effect (NOE) spectroscopy data. To build the model, the NMR-based theoretical conformational analysis of synthetic PND peptides of length 40, 24, and 12 residues is carried out. The modeling of the molecular spatial structures is performed by a new approach to research of conformationally mobile peptides using the algorithms of the restrained molecular mechanics method developed earlier. The following major conclusions are made based on the analysis of the simulated peptide conformations: i) there is not unique PND structure in solution, ii) there are seven different PND structures each of which agrees with the experimental data and stereochemical criteria used in computing its spatial model, iii) the PND is characterized by irregular conformation containing a number of reverse turns, iv) all of the selected conformations are conserved in the Gly-Pro-Gly-Arg-Ala-Phe stretch, the most probable viral immunodominant epitope. These data allow to suppose that binding properties of this site are determined by the structural motif which forms the conformation of a double beta-turn and appears common for all hexapeptide structures.

HIV Envelope Protein gp120↗
PubMed1998

Spatial structure model of the CD4 receptor-binding site of the HIV envelope protein gp120.

In this study we have undertaken attempt to predict 3D structure of the CD4 receptor-binding site of the HIV envelope protein gp120. The structure of this site has been constructed by the analysis of low-energy conformers of peptide T, an HIV reproduction inhibitor with amino acid sequence corresponding to the fragment Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr of protein gp120, ensuring the interaction of virus with T4 lymphocytes. To do this, the following researches have been carried out: i) the spatial structure models of peptide T and similar fragment 4-11 of an analogues of vasoactive intestinal peptide have been modeled by the restrained molecular mechanics method developed earlier, ii) conformational parameters of these models have been compared to geometrical characteristics of homologous segments of unrelated proteins with known spatial structures. The following major conclusions have been made based on the comparative analysis: i) the conformation of C-terminal fragment Thr-Thr-Asn-Tyr-Thr of peptide T, responsible for the biological activity of the molecule, does not undergo the essential distortions while embedding into the peptide chains of unrelated proteins; ii) this conformation, that is realized in isolated molecule and includes two consecutive reverse turns of the polypeptide chain, adequately describes the main conformational features of an appropriate site of the HIV protein gp120; iii) the fragment Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr of protein gp120 accepts one of six spatial forms which are characteristic for peptide T.

Binding Sites↗
PubMed1988

Method of modeling protein structure by the two-dimensional nuclear magnetic resonance spectroscopy data; application to the proteinase inhibitor BUSI IIA from bull seminal plasma.

A new approach is suggested to model the spatial structure of protein molecules in solution based on combined use of the methods of theoretical conformational analysis and NMR spectroscopy data. At the first stage, special means are used to convert d connectivity information into the most probable values of dihedral angles. This allows search for possible spatial structures in the limited regions of the conformational space at further stages using the methods of the theoretical conformational analysis. The suggested approach was verified in reconstructing the spatial backbone structure of the fragment 17-57 of the proteinase inhibitor BUSI IIA from the bull seminal plasma. The structural model parameters are compared with the corresponding characteristics obtained from the X-ray analysis data for the homologic proteinase inhibitor from the Japanese quail ovomucoid. The suggested approach is shown to correctly reproduce both the general molecule topology and the conformations of individual amino acid residues.

Amino Acid Sequence↗
PubMed1987

Method of determining protein conformations by the two-dimensional nuclear Overhauser enhancement spectroscopy data.

A method is suggested to determine the most probable values of the angles phi, psi of the protein backbone by the data on the availability and absence of d connectivities in the two-dimensional nuclear Overhauser enhancement spectra. In view of this, the dependences of the proton-proton distances in dipeptide units of L-amino acid residues on the dihedral angles phi, psi, chi1 are considered and the conformational states of amino acid residues of the proteins with the known spatial structure are analysed statistically. The potentialities of the method are assessed with the aid of model spectral nuclear magnetic resonance (NMR) parameters obtained from the X-ray data for the bovine pancreatic trypsin inhibitor and avian pancreatic polypeptide. It is shown that the developed procedure of structural interpretation of the NMR data allows one to correctly reproduce the local conformation of the protein backbone. The obtained backbone conformation may serve as a starting point to build and refine molecular three-dimensional structure.

Aprotinin↗
PubMedDate not supplied

[Isolation of iodine-protein components from sea algae].

The isolation of iodorganic compounds from the Black Sea red alga Phyllophora nervosa and its by-products obtained from industrial treatment was investigated. The algal biomass was pressed to remove alkali, subjected to 5-10 min treatment with 11-12% sodium hydrate, and drying at 125-130 degrees C and washed to yield 95% iodine and over 80% proteins. Iodine was found to be bound with protein of Phyllophora. Properties of the isolated iodine-peptide fractions were studied.

Amino Acids↗
PubMedDate not supplied

[Spatial structure of the rp142 peptide containing the immunodominant epitope of the HIV-1 gp120 protein. A theoretical study].

A model of spatial structure of the synthetic peptide rp142 (24 amino acid residues) containing the immunodominant epitope of the HIV-1 protein gp120 in the region Gly-10-Phe-15 was constructed by the method of "constrained" molecular mechanics, which uses the algorithms of theoretical conformational analysis, based on NMR spectroscopy data. A comparative analysis of calculated conformations revealed that the spatial structure of rp142 in solution can be described by a family of conformations to which nine different structural clusters involving the sets of topologically close conformers correspond. It is shown that the main chain of the peptide forms irregular but "structured" conformations in which the main portion of amino acid residues is incorporated into beta-turns and helix-like fragments, while Pro-11 and Gly-12 form in some structures inverse gamma-turns, which rarely occur in protein-peptide molecules. It was found that the spatial packing of the Gly-10-Phe-15 hexapeptide in different clusters is realized at different internal rotation angles, to which topologically close structures correspond. It is assumed that this invariant structural element describes the "conformation of complex formation" that is complementary to the antigen-binding center of antibodies and is responsible for their binding to the peptide.

Amino Acid Sequence↗