Počet záznamů: 1
Interface Interactions of the Bowman-Birk Inhibitor BTCI in a Ternary Complex with Trypsin and Chymotrypsin Evaluated by Semiempirical Quantum Mechanical Calculations
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SYSNO ASEP 0495770 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Interface Interactions of the Bowman-Birk Inhibitor BTCI in a Ternary Complex with Trypsin and Chymotrypsin Evaluated by Semiempirical Quantum Mechanical Calculations Tvůrce(i) Honda, D. E. (BR)
Martins, J. B. L. (BR)
Ventura, M. M. (BR)
Eyrilmez, Saltuk M. (UOCHB-X) ORCID, RID
Lepšík, Martin (UOCHB-X) RID, ORCID
Hobza, Pavel (UOCHB-X) RID, ORCID
Pecina, Adam (UOCHB-X) RID, ORCID
de Freitas, S. M. (BR)Zdroj.dok. European Journal of Organic Chemistry - ISSN 1434-193X
Roč. 2018, č. 37 (2018), s. 5203-5211Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova protein-protein interactions ; protease inhibitors ; protein structures ; interaction energy ; amino acids ; interfaces Vědní obor RIV CF - Fyzikální chemie a teoretická chemie Obor OECD Physical chemistry CEP EF16_019/0000729 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000446662900014 EID SCOPUS 85052623049 DOI 10.1002/ejoc.201800754 Anotace Black-eyed pea trypsin and chymotrypsin inhibitor (BTCI) is a small protein from Bowman-Birk protease inhibitor family, which simultaneously inhibits trypsin and chymotrypsin. Through the inhibition of trypsin- and chymotrypsin-like sites on the 20S subunit of human proteasome, BTCI acts as a potent anticarcinogenic agent inducing apoptosis in breast cancer cells. Because of the lack of crystallographic information of the BTCI-proteasome complex, we analyze here the BTCI-chymotrypsin and BTCI-trypsin interfaces using computations. We adopt the corrected semiempirical quantum-mechanical methods in combination with implicit description of the water environment. Firstly, we carefully check the representativeness of smaller systems by fragmentation and analyzing the convergence of the overall interaction energies. Then, we use the virtual glycine scan technique to understand the binary complex formation, identifying the most contributing amino acid side chains in the interfaces. Besides detailed quantification of all important residue contributions, the importance of Lys26 and Phe53 in the BTCI and Asp186 (trypsin) and Ser195 (chymotrypsin) residues is confirmed. In summary, we have worked out an accurate and efficient in silico protocol for protein-protein interfaces, which can be later used for studying the inhibition of 20S proteasome. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2019
Počet záznamů: 1