Modification of quaternary structure of Candida albicans GlcN-6-P synthase and its desensitization to inhibition by UDP-GlcNAc by site-directed mutagenesis - Publikacja - MOST Wiedzy

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Modification of quaternary structure of Candida albicans GlcN-6-P synthase and its desensitization to inhibition by UDP-GlcNAc by site-directed mutagenesis

Abstrakt

Site-directed mutagenesis of the CaGFA1 gene encoding glucosamine-6-phosphate synthase from Candida albicans was performed. Desensitization of the enzyme to inhibition by UDPGlcNAc was achieved upon T487I and H492F substitutions at the UDP-GlcNAc binding site, exchange of D524, S525 and S527 for Ala at the dimer:dimer interface and construction of the tail-lock array (L434R and L460A) at the C-tail region. The first two sets if mutageneses but not the last one resulted in conversion of the tetrameric enzyme into its dimeric form. Evidence for links and communication between the UDP-GlcNAc binding site and the imer-dimer contact areas are presented. The CaGfa1-T487IH492F and CaGfa1-KHSH-D524AS525AS527A muteins are the first examples of the successful conversion of eukaryotic GlcN-6-P synthase into its prokaryotic-like version upon rational sitedirected mutagenesis.

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Kategoria:
Publikacja w czasopiśmie
Typ:
artykuł w czasopiśmie wyróżnionym w JCR
Opublikowano w:
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS nr 1866, wydanie 11, strony 1181 - 1189,
ISSN: 1570-9639
Język:
angielski
Rok wydania:
2018
Opis bibliograficzny:
Kwiatkowska-Semrau K., Wojciechowski M., Gabriel I., Crucho S., Milewski S.: Modification of quaternary structure of Candida albicans GlcN-6-P synthase and its desensitization to inhibition by UDP-GlcNAc by site-directed mutagenesis// BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS. -Vol. 1866, iss. 11 (2018), s.1181-1189
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1016/j.bbapap.2018.08.003
Weryfikacja:
Politechnika Gdańska

wyświetlono 136 razy

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