Evgeny V. Grishin D. sc. (chemistry), professor, member of the academy of sciences Deputy sci-director (direction), director of departament (laboratory of neuroreceptors and neuroregulators) Phone: +7 (495) 330-58-92, +7 (495) 336-65-40, E-mail: grev@mx.ibch.ru

Personal information

Deputy director of Shemiakin-Ovchinnikov Institute of bioorganic chemistry RAS; the head of laboratory; professor of Moscow State University; Doctor Honoris Causa of Universidad Nacional Mayor de San Marcos and Universidad Ricardo Palma (Lima, Peru).

Education

Selected publications

1. Ryazantsev D.Y.u., Petrova E., Kalinina N.A., Valyakina T.I., Grishin E.V., Zavriev S.K. (2009). Application of supramolecular DNA-streptavidin complexes for ultrasensitive detection of several toxins by immuno-PCR. 14. Global J. Anal. Chem. 3 (17), [+]
   
2. Andreev Y.A., Kozlov S.A., Koshelev S.G., Ivanova E.A., Monastyrnaya M.M., Kozlovskaya E.P., Grishin E.V. (2008). Analgesic compound from sea anemone Heteractis crispa is the first polypeptide inhibitor of vanilloid receptor 1 (TRPV1). J. Biol. Chem. 283 (35), 23914–21 [+]

   The first inhibitor of thermoreceptors TRPV1 that play an important role in inflammation and pain sensation was isolated from nematocyst extract of the sea anemone Heteractis crispa. Recombinant analogue of the peptide named APHC1 was found to exert high analgesic activity comparable to that of opioids in vivo. Unlike opioids, however, the action of APHC1 does not lead to a narcotic effect. The newly described polypeptide has great practical value in terms of new analgesic and anti-inflammatory drug production.

3. Kozlov S.A., Vassilevski A.A., Feofanov A.V., Surovoy A.Y., Karpunin D.V., Grishin E.V. (2006). Latarcins, antimicrobial and cytolytic peptides from the venom of the spider Lachesana tarabaevi (Zodariidae) that exemplify biomolecular diversity. J. Biol. Chem. 281 (30), 20983–92 [+]

   A family of short linear polypeptide molecules, latarcins, was found in the venom of the spider Lachesana tarabaevi. Some peptides were chemically synthesized and their antimicrobial properties were studied. The bactericidal activity of latarcins matched that of the most active known antimicrobial peptides from different animals. The high therapeutic potential of these structurally simple polypeptide molecules will be brought to clinic in the near future.

4. Kozlov S., Malyavka A., McCutchen B., Lu A., Schepers E., Herrmann R., Grishin E. (2005). A novel strategy for the identification of toxinlike structures in spider venom. Proteins 59 (1), 131–40 [+]

   We compared two different approaches to sequence information analysis from the expressed sequence tag (EST) library constructed for the venom glands of the spider Agelena orientalis. Some results were more illustrative and reliable by the contig analysis technique, whereas our novel method, with specific structural markers introduced for protein structure detection, allowed us to overcome some limitations of the contig analysis. A novel technique was suggested for the identification in data banks of the spider's ion channel inhibitor toxins using primary structure features common to all spiders. Analysis of about 150 polypeptides made it possible to introduce 3 primary structure motifs for spider toxins: the Principal Structural Motif (PSM), which postulates the existence of 6 amino acid residues between the first and second cysteine residue and the Cys-Cys sequence at a distance of 5-10 amino acid residues from the second cysteine; the Extra Structural Motif (ESM), which postulates the existence of a pair of CXC fragments in the C-region; and the Processing Quadruplet Motif (PQM), which specifies the Arg residue at position -1 and Glu residues at positions -2, -3, and/or -4 in the precursor sequences just before the postprocessing site. In the processed data bank we found 48 toxinlike structures with ion channel inhibitor motifs. These include agelenin earlier isolated from Agelena opulenta and 25 more homologous sequences, 15 homologs of mu-agatoxin 2 from the spider Agelenopsis aperta, 3 structures with low homology to omega-agatoxin-IIIA, and 4 new structures. Also we showed that toxinlike structures exceed two thirds of the overall database sequences.

5. Korolkova Y.V., Bocharov E.V., Angelo K., Maslennikov I.V., Grinenko O.V., Lipkin A.V., Nosyreva E.D., Pluzhnikov K.A., Olesen S.P., Arseniev A.S., Grishin E.V. (2002). New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1. J. Biol. Chem. 277 (45), 43104–9 [+]

   The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.

6. Korolkova Y.V., Kozlov S.A., Lipkin A.V., Pluzhnikov K.A., Hadley J.K., Filippov A.K., Brown D.A., Angelo K., Strøbaek D., Jespersen T., Olesen S.P., Jensen B.S., Grishin E.V. (2001). An ERG channel inhibitor from the scorpion Buthus eupeus. J. Biol. Chem. 276 (13), 9868–76 [+]

   The first selective blocker of K⁺ channels of ERG type BeKm was isolated from the venom of the scorpion Buthus eupeus. The peptide along with its mutants was produced in a heterological expression system and their properties were assessed on M-currents in the NG108-15 cell line, which allowed establishing the peptide’s pharmacophore. BeKm toxin became the first published selective inhibitor of hERG channels. At present it may be found on the market of bioactive substances.

7. Grishin E.V. (1999). Polypeptide neurotoxins from spider venoms. Eur. J. Biochem. 264 (2), 276–80 [+]

   Spider venoms contain a variety of toxic components. The polypeptide toxins are divided into low and high molecular mass types. Small polypeptide toxins interacting with cation channels display spatial structure homology. They can affect the functioning of calcium, sodium, or potassium channels. A family of high molecular mass toxic proteins was found in the venom of the spider genus Latrodectus. These neurotoxins, latrotoxins, cause a massive transmitter release from a diversity of nerve endings. The latrotoxins are proteins of about 1000 amino acid residues and share a high level of structure identity. The structural and functional properties of spider polypeptide toxins are reviewed in this paper.

8. Lelianova V.G., Davletov B.A., Sterling A., Rahman M.A., Grishin E.V., Totty N.F., Ushkaryov Y.A. (1997). Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J. Biol. Chem. 272 (34), 21504–8 [+]

   Ca²⁺-independent receptor of α-latrotoxin, latrophilin was discovered and studied. The protein was found to be a novel G protein-coupled receptor of the secretin family that plays an important role in neuromediator secretion. Analyses of its function and regulation by endogenic ligands are crucial for deciphering the mechanism of synaptic vesicle exocytosis.

9. Kiyatkin N.I., Dulubova I.E., Chekhovskaya I.A., Grishin E.V. (1990). Cloning and structure of cDNA encoding alpha-latrotoxin from black widow spider venom. FEBS Lett. 270 (1-2), 127–31 [+]

   The primary structure of α-latrotoxin from the venom of black widow spider Latrodectus mactans that possesses a unique ability to stimulate neromediator secretion from the neural termini of vertebrate animals and shows markedly high toxicity to mammals is reported in this paper. Full amino acid sequence of the ~130 kDa toxin was established.

10. Ovchinnikov Yu.A., Egorov C.A., Aldanova N.A., Feigina M.Y., Lipkin V.M., Abdulaev N.G., Grishin E.V., Kiselev A.P., Modyanov N.N., Braunstein A.E., Polyanovsky O.L., Nosikov V.V. (1973). The complete amino acid sequence of cytoplasmic aspartate aminotransferase from pig heart. FEBS Lett. 29 (1), 31–34 [+]

    Aspartate aminotransferase (L-aspartate: 2-oxo-glutarate aminotransferase, EC 2.6.1.1) is one of the principal pyridoxal-P-containing enzymes that catalyse the transamination reactions [3] representing key steps
    at the intersection between the metabolic pathways of amino acids and dicarboxylic acids.
    Although the catalytic mechanism of aspartate aminotransferase has been investigated at the level of substrate-coenzyme models [4], its elucidation in detail requires knowledge of the enzyme’s structure, considering, in particular, that the very high rates of the enzymic process are determined by the structural peculiarities of the specific protein(apoenzyme) of the aspartate aminotransferase. Accordingly, we embarked
    on the task of elucidating the amino acid sequence of this enzyme. In the present paper the concluding stage
    of the work is reported*. The object chosen for study was the aspartate aminotransferase
    of the cytosol of pig heart; the enzyme, which is different from the mitochondrial isozyme
    [5,6] was prepared by a previously reported procedure [7]. The enzyme is a complex dimeric protein of
    high molecular weight; each of the associated subunits consists of a single polypeptide chain and has no disulfide bridges. Indirect evidence (amino acid composition, analysis of N-terminal residues, and peptide maps) testified to the identity of the two subunits [8].