Zakhar Shenkarev

The laboratory investigates membrane receptors and ion channels, as well as compounds acting on them (toxins, endogenous ligands). To study the structure and mechanisms of action at the molecular level, we use modern methods of structural biology: NMR spectroscopy and cryoelectron microscopy. We are currently studying the mechanisms of interaction of toxins with voltage-dependent K+ and Na+ channels (Kv and Nav), as well as studying the structures of protein ligands of the nicotinic acetylcholine receptor (nAChR). Structural studies of membrane receptors and channels are necessary for the development of new diagnostic tools and therapy for diseases of the nervous, cardiovascular, and muscular systems of the body. In addition, we study the structures and mechanisms of action of antibiotics and protective peptides in plants and animals. These studies are needed to create new drugs for the treatment of infectious diseases.

1.Shulepko MA, Bychkov ML, Shenkarev ZO, Kulbatskii DS, Makhonin AM, Paramonov AS, Chugunov AO, Kirpichnikov MP, Lyukmanova EN. Biochemical Basis of Skin Disease Mal de Meleda: SLURP-1 Mutants Differently Affect Keratinocyte Proliferation and Apoptosis. J Invest Dermatol. 2021 Sep;141(9):2229-2237. doi: 10.1016/j.jid.2021.01.035. Epub 2021 Mar 16. PMID: 33741389.

2.Tyurin AP, Alferova VA, Paramonov AS, Shuvalov MV, Kudryakova GK, Rogozhin EA, Zherebker AY, Brylev VA, Chistov AA, Baranova AA, Biryukov MV, Ivanov IA, Prokhorenko IA, Grammatikova NE, Kravchenko TV, Isakova EB, Mirchink EP, Gladkikh EG, Svirshchevskaya EV, Mardanov AV, Beletsky AV, Kocharovskaya MV, Kulyaeva VV, Shashkov AS, Tsvetkov DE, Nifantiev NE, Apt AS, Majorov KB, Efimova SS, Ravin NV, Nikolaev EN, Ostroumova OS, Katrukha GS, Lapchinskaya OA, Dontsova OA, Terekhov SS, Osterman IA, Shenkarev ZO, Korshun VA. Gausemycins A,B: Cyclic Lipoglycopeptides from Streptomyces sp.*. Angew Chem Int Ed Engl. 2021 Aug 16;60(34):18694-18703. doi: 10.1002/anie.202104528. Epub 2021 Jun 22. PMID: 34009717.

3.Bolosov IA, Panteleev PV, Sychev SV, Sukhanov SV, Mironov PA, Myshkin MY, Shenkarev ZO, Ovchinnikova TV. Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins. Front Microbiol. 2021 Aug 13;12:725526. doi: 10.3389/fmicb.2021.725526. PMID: 34484167; PMCID: PMC8415029.

4.Paramonov AS, Kocharovskaya MV, Tsarev AV, Kulbatskii DS, Loktyushov EV, Shulepko MA, Kirpichnikov MP, Lyukmanova EN, Shenkarev ZO. Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors. Int J Mol Sci. 2020 Oct 1;21(19):7280. doi: 10.3390/ijms21197280. PMID: 33019770; PMCID: PMC7582953.

5.Shenkarev ZO, Shulepko MA, Bychkov ML, Kulbatskii DS, Shlepova OV, Vasilyeva NA, Andreev-Andrievskiy AA, Popova AS, Lagereva EA, Loktyushov EV, Koshelev SG, Thomsen MS, Dolgikh DA, Kozlov SA, Balaban PM, Kirpichnikov MP, Lyukmanova EN. Water-soluble variant of human Lynx1 positively modulates synaptic plasticity and ameliorates cognitive impairment associated with α7-nAChR dysfunction. J Neurochem. 2020 Oct;155(1):45-61. doi: 10.1111/jnc.15018. Epub 2020 May 10. PMID: 32222974.

6.Myshkin MY, Männikkö R, Krumkacheva OA, Kulbatskii DS, Chugunov AO, Berkut AA, Paramonov AS, Shulepko MA, Fedin MV, Hanna MG, Kullmann DM, Bagryanskaya EG, Arseniev AS, Kirpichnikov MP, Lyukmanova EN, Vassilevski AA, Shenkarev ZO. Cell-Free Expression of Sodium Channel Domains for Pharmacology Studies. Noncanonical Spider Toxin Binding Site in the Second Voltage-Sensing Domain of Human Nav1.4 Channel. Front Pharmacol. 2019 Sep 4;10:953. doi: 10.3389/fphar.2019.00953. PMID: 31555136; PMCID: PMC6737007.

7.Männikkö R, Shenkarev ZO, Thor MG, Berkut AA, Myshkin MY, Paramonov AS, Kulbatskii DS, Kuzmin DA, Sampedro Castañeda M, King L, Wilson ER, Lyukmanova EN, Kirpichnikov MP, Schorge S, Bosmans F, Hanna MG, Kullmann DM, Vassilevski AA. Spider toxin inhibits gating pore currents underlying periodic paralysis. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4495-4500. doi: 10.1073/pnas.1720185115. Epub 2018 Apr 10. PMID: 29636418; PMCID: PMC5924911.