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Importance of N-terminal proline for the promiscuous activity of 4-oxalocrotonate tautomerase (4-OT)
dc.creator | Lazić, Jelena O. | |
dc.creator | Spasić, Jelena | |
dc.creator | Francuski, Đorđe | |
dc.creator | Tokić-Vujošević, Zorana | |
dc.creator | Nikodinović-Runić, Jasmina | |
dc.creator | Maslak, Veselin | |
dc.creator | Đokić, Lidija | |
dc.date.accessioned | 2018-11-22T00:37:00Z | |
dc.date.available | 2018-11-22T00:37:00Z | |
dc.date.issued | 2016 | |
dc.identifier.issn | 0352-5139 | |
dc.identifier.uri | https://cherry.chem.bg.ac.rs/handle/123456789/2324 | |
dc.description.abstract | Michael addition of aldehydes to nitro-olefins is an effective method to obtain useful chiral gamma-nitroaldehydes. gamma-Nitroaldehydes are precursors for chiral gamma-aminobutyric acid analogues, which have numerous pharmacological activities and are used for the treatment of neurological disorders. A whole-cell system based on recombinantly expressed 4-oxalocrotonate tautomerase (4-OT) was developed and shown to be an effective biocatalyst for the Michael addition of branched aldehydes to beta-nitrostyrenes. The aim of this study was to investigate the influence of the substitution of the N-terminal proline with lysine and arginine, both containing a reactive epsilon-amino group, on the Michael addition catalyzed by 4-OT. First, the effects of these mutations were examined by in silico analysis, followed by the generation of three terminal lysine mutants. The generated mutants, 4-OT_K, 4-OT_PK and 4-OT_KK were tested for their ability to utilise beta-nitrostyrene (1), (E)-1-nitro-2-(2-thienyl)ethene (2) and trans-p-chloro-beta-nitrostyrene (3) as Michael acceptors with isobutanal (2-methylpropanal) as the donor. For comparison, the lithium salt of lysine was used in the same organocatalytic reactions. In general, the introduction of lysine had a negative effect on Michael additions based on overall product yields. However, additional lysine residues at the N-terminus of the protein resulted in structural changes that enhanced the activity towards 2 and 3. Therefore, the N-terminal proline is important for 4-OT-catalysed Michael-additions, but it is not essential. | en |
dc.publisher | Serbian Chemical Soc, Belgrade | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173048/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172002/RS// | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Journal of the Serbian Chemical Society | |
dc.subject | 4-oxalocrotonate tautomerase | en |
dc.subject | biocatalysis | en |
dc.subject | organocatalysis | en |
dc.subject | lysine | en |
dc.subject | mutagenesis | en |
dc.title | Importance of N-terminal proline for the promiscuous activity of 4-oxalocrotonate tautomerase (4-OT) | en |
dc.type | article | |
dc.rights.license | BY-NC-ND | |
dcterms.abstract | Токиц-Вујосевиц, Зорана; Француски, Дјордје; Спасиц, Јелена; Лазиц, Јелена; Дјокиц, Лидија; Никодиновић-Рунић, Јасмина; Маслак, Веселин; | |
dc.citation.volume | 81 | |
dc.citation.issue | 8 | |
dc.citation.spage | 871 | |
dc.citation.epage | 881 | |
dc.identifier.wos | 000384930600003 | |
dc.identifier.doi | 10.2298/JSC160222053L | |
dc.citation.other | 81(8): 871-881 | |
dc.citation.rank | M23 | |
dc.type.version | publishedVersion | |
dc.identifier.scopus | 2-s2.0-84987792424 | |
dc.identifier.fulltext | https://cherry.chem.bg.ac.rs/bitstream/id/9307/2322.pdf |