Valery M. Lipkin

Personal information

The position is a post-graduate student, a junior scientific researcher, a senior scientific researcher (1965—1986); the head of the laboratory of hormonal regulation proteins (1986—to present day); the deputy director (1987—2008); the head of the Institute’s Pushchino Branch (1987—2004).

Doing educational work in Pushchino state university, dean of physico-chemical biology and biotechnology EC, MPTI, department of physico-chemical biology and biotechnology as hourly teacher.

Education

PeriodCountry, cityEducation institutionAdditional info
1959–1964 Russia, Moscow D.I. Mendeleev Moscow chemical-engineering Institute engineer-technologist (chemistry)
1982 Russia, Moscow D.Sc. in chemistry (bioorganic chemistry)

Scientific interests

Top-level specialist in protein and peptide chemistry. Dr. V. Lipkin goes in for investigations of the proteins, involved in transmembrane signal transduction, cells differentiation and apoptosis.

Awards & honors

  • 1975: Leninskiy Komsomol Prize;
  • 1981: Order of International friendship;
  • 1982: USSR State Prize;
  • 1997: Yu.A. Ovchinnikov Prize.

Main scientific results

V.M. Lipkin was a member of a team under the leadership of Academician Yu.A. Ovchinnikov, which in 1972 for the first time in our country determined the amino acid sequence of the protein — aspartat aminotransferase. In 1975—1985 V.M. Lipkin was engaged in the investigation of E. coli DNA-dependent RNA-polymerase. In cooperation with the colleagues he has determined amino acid sequences of all subunits of the enzyme, elaborated methods of chemical and photochemical affine modification of its active centers, elucidated the molecular mechanism of RNA-polymerase inhibition by riphampycin antibiotic. The investigations contributed significantly to clarification of transcription mechanisms.

Scientific societies’ membership

  • Editorial Board member of “Russian Journal of Bioorganic Chemistry”;
  • Member of RAS Scientific Council in bioorganic chemistry.

Selected publications

  1. Rzhevsky D.I., Zhokhov S.S., Babichenko I.I., Goleva A.V., Goncharenko E.N., Baizhumanov A.A., Murashev A.N., Lipkin V.M., Kostanyan I.A. (2005). HLDF-6 peptide affects behavioral reactions and organism functions dependent on androgen hormones in normal and castrated male mice. Regul. Pept. 127 (1-3), 111–21 [+]

    The hexapeptide Thr-Gly-Glu-Asn-His-Arg (HLDF-6), which was first identified as an active fragment of the human leukemia differentiation factor (HLDF) molecule, displays differentiation-inducing, neuroprotective and anti-drug abuse activities. Most of its in vivo effects were revealed only on male animals. We have studied HLDF-6 effects on a variety of organism functions and behavioral reactions, which are known to be dependent on androgen steroid hormones, both on castrated and normal (sham-operated) animals. Male NMRI mice were castrated or sham-operated at the age of 55 days (after puberty). After that, HLDF-6 peptide was injected daily during 3 weeks, followed by behavioral, morphological and biochemical testing. HLDF-6 increased testosterone level (1.5- to 2-fold) both in sham-operated and castrated animals. Sexual activity and pain sensitivity, which are strongly reduced in castrates, were completely or partially recovered by HLDF-6. At the same time, the peptide caused some effects similar to castration in sham-operated animals: aggression and locomotor activity were decreased; oral grooming was prolonged. Morphological studies of accessory sex glands showed that HLDF-6 partially normalizes the morphology and functional activity of seminal vesicles in castrates, but it does not prevent castration-induced apoptosis of prostate epithelial cells. Based on these observations, we can assume that HLDF-6 peptide displays at least two effects on androgen hormones metabolism in males: it stimulates testosterone biosynthesis by both testes and adrenals and simultaneously inhibits its conversion to dihydrotestosterone (DHT), most probably by diminution of 5alpha-reductase isoform 1 mRNA expression.

  2. Merkulova M.I., Andreeva S.G., Shuvaeva T.M., Novoselov S.V., Peshenko I.V., Bystrova M.F., Novoselov V.I., Fesenko E.E., Lipkin V.M. (1999). A novel 45 kDa secretory protein from rat olfactory epithelium: primary structure and localisation. FEBS Lett. 450 (1-2), 126–30 [+]

    cDNA clones encoding the 45 kDa protein were isolated from a rat olfactory epithelium cDNA library and their inserts were sequenced. The reconstructed protein sequence comprises 400 amino acids with a calculated molecular mass of 46,026 Da. A homology was revealed between the amino acid sequence of the 45 kDa protein and the proteins involved in the transfer of hydrophobic ligands. Using in situ hybridisation, the 45 kDa protein mRNA expression was detected in the layer of supportive cells of olfactory epithelium, apical region of trachea, surface layer of the ciliated bronchial epithelium in lung and in skin epidermis.

  3. Kostanyan I.A., Astapova M.V., Starovoytova E.V., Dranitsina S.M., Lipkin V.M. (1994). A new human leukemia cell 8.2 kDa differentiation factor: isolation and primary structure. FEBS Lett. 356 (2-3), 327–9 [+]

    A new 8.2 kDa differentiation factor has been purified to homogeneity from the cultural media of human myelogenous HL-60 leukemia cells induced by retinoic acid. cDNA clones encoding this factor were isolated from a cDNA library prepared from HL-60 differentiated cells and their nucleotide sequence has been determined. The deduced amino acid sequence of the differentiation factor molecule consists of 54 amino acid residues. The protein is shown to be glycosylated. It was shown by Northern blot experiments that the level of poly(A)+ RNA with a length of 450 nucleotides was higher in differentiated cells than in non-differentiated cells.

  4. Khramtsov N.V., Feshchenko E.A., Suslova V.A., Shmukler B.E., Terpugov B.E., Rakitina T.V., Atabekova N.V., Lipkin V.M. (1993). The human rod photoreceptor cGMP phosphodiesterase beta-subunit. Structural studies of its cDNA and gene. FEBS Lett. 327 (3), 275–8 [+]

    cDNA clones encoding the beta-subunit of the photoreceptor cGMP phosphodiesterase (PDE) were isolated from a human retina library and their sequence was determined. The encoded polypeptide consists of 854 amino acid residues with a calculated molecular mass of 98,416 Da. Alignment of the deduced amino acid sequence with the earlier analysed alpha-, beta- and alpha'-subunits of bovine and mouse PDEs demonstrates a high homology. Two overlapping recombinant lambda phage clones containing 26 kb of the human PDE beta-subunit gene were isolated from the genomic library. A total nucleotide sequence of exons 4-22 of the PDE beta-subunit gene was established which completely corresponded to the cDNA structure. According to sequence analysis no potential possibility for alternative splicing of the beta-subunit gene was observed between exons 20 and 21 which led to the formation of the beta'-subunit as described for mouse PDE. Polymerase chain reaction (PCR) experiments also confirm the absence of the PDE beta'-subunit in human retina.

  5. Lipkin V.M., Khramtsov N.V., Vasilevskaya I.A., Atabekova N.V., Muradov K.G., Gubanov V.V., Li T., Johnston J.P., Volpp K.J., Applebury M.L. (1990). Beta-subunit of bovine rod photoreceptor cGMP phosphodiesterase. Comparison with the phosphodiesterase family. J. Biol. Chem. 265 (22), 12955–9 [+]

    A group of cDNA clones encoding the beta-subunit of bovine rod photoreceptor cGMP phosphodiesterase were isolated for structural analysis. The encoded polypeptide has 853 residues with a calculated molecular mass of 98 kDa. The beta-subunit is 72% identical to the rod cGMP phosphodiesterase alpha-subunit. Like the alpha-subunit and the cone alpha'-subunit, the beta-subunit belongs to the family of phosphodiesterase genes. The beta- and alpha-subunits are more similar to each other than either is to the cone alpha'-subunit, suggesting either that the beta- and alpha-subunits diverged more recently or that their divergence was restrained by the rod functional environment.

  6. Ovchinnikov Yu.A., Lipkin V.M., Shuvaeva T.M., Bogachuk A.P., Shemyakin V.V. (1985). Complete amino acid sequence of gamma-subunit of the GTP-binding protein from cattle retina. FEBS Lett. 179 (1), 107–10 [+]

    The complete amino acid sequence of the gamma-subunit of the GTP-binding protein from cattle retina has been established. The polypeptide chain of the gamma-subunit consists of 69 amino acid residues and contains the unusual sequence Cys35-Cys36. The Mr of the gamma-subunit is 8008.7.

  7. Ovchinnikov Yu.A., Monastyrskaya G.S., Gubanov V.V., Guryev S.O., Salomatina I.S., Shuvaeva T.M., Lipkin V.M., Sverdlov E.D. (1982). The primary structure of E. coli RNA polymerase, Nucleotide sequence of the rpoC gene and amino acid sequence of the beta'-subunit. Nucleic Acids Res. 10 (13), 4035–44 [+]

    The primary structure of the E. coli rpoC gene (5321 base pairs) coding the beta'-subunit of RNA polymerase as well as its adjacent segment have been determined. The structure analysis of the peptides obtained by cleavage of the protein with cyanogen bromide and trypsin has confirmed the amino acid sequence of the beta'-subunit deduced from the nucleotide sequence analysis. The beta'-subunit of E. coli RNA polymerase contains 1407 amino acid residues. Its translation is initiated by codon GUG and terminated by codon TAA. It has been detected that the sequence following the terminating codon is strikingly homologous to known sequences of rho-independent terminators.

  8. Овчинников Ю.А., Липкин В.М., Модянов Н.Н., Чертов О.Ю., Смирнов Ю.В., Хохряков В.С., Шуваева Т.М. (1977). ДНК-зависимая РНК-полимераза E.coli. Полная аминокислотная последовательность альфа-субъединицы. Биоорг. хим. 3 (1), 283–286
  9. Ovchinnikov Yu.A., Lipkin V.M., Modyanov N.N., Chertov O.Y., Smirnov Y.V. (1977). Primary structure of alpha-subunit of DNA-dependent RNA polymerase from Escherichia coli. FEBS Lett. 76 (1), 108–11 [+]

    Transcription of genetic information in bacterial cells is mediated by DNA-dependent RNA polymerase (ribonucleoside-triphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) [ 11. The enzyme from E. coli
    (mol. wt 500 000) has been shown to possess a complex structure [2] consisting of two large subunits, /?
    and 0’ (mol. wt 155 000 and 16.5 000, respectively), two a-subunits (mol. wt 40 000) and initiation factor,
    u (mol. wt 90 000). Its structural complexity is paralleled by the multistep nature of the transcription
    process. Only limited information on the role of the individual subunits in the functioning of RNA polymerase
    is available, owing in part to our lack of knowledge of its primary and spatial structure. We have, therefore,
    undertaken an investigation into the primary structure of DNA-dependent RNA polymerase from
    E. coli B. In the study reported here we have determined the complete amino acid sequence of the RNA poly
    merase a-subunit (see [3] ) using a variety of degradation methods and i4C-enriched amino acid residues
    for facilitating detection and isolation of the fragments. The polypeptide chain of the o-subunit has mol. w
    36 512 and consists of 329 amino acid residues. In a comparative study of the peptide compositions of
    various bacterial polymerase a-subunits it has been shown by peptide mapping that they are evolutionarily
    conservative proteins [4].

  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].

  11. Shemyakin M.M., Ovchinnikov Yu.A., Kiryushkin A.A., Vinogradova E.I., Miroshnikov A.I., Alakhov Yu.B., Lipkin V.M., Shvetsov Yu.B., Wulfson N.S., Rosinov B.V., Bochkarev V.N., Burikov V.M. (1966). Mass spectrometric determination of the amino-acid sequence of peptides. Nature 211 (5047), 361–6 [+]

    New method of determination polypeptide amino acids sequenses with mass-spectoscopy of acyl ethers. This method base on peptide fragmentation with localizing positive charge on N-acyl fragments.