Functional analysis on a naturally occurring variant of the Staphylococcus Aureus uracil DNA Glycosylase inhibitor

Papp-Kádár, Veronika and Balázs, Zoltán and Nagy, Gergely N. and Juhász, Tünde and Liliom, Károly and G. Vértessy, Beáta (2018) Functional analysis on a naturally occurring variant of the Staphylococcus Aureus uracil DNA Glycosylase inhibitor. PERIODICA POLYTECHNICA-CHEMICAL ENGINEERING, 62 (1). pp. 51-56. ISSN 0324-5853

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Abstract

Repair of DNA damage relies on various pathways including the base excision repair (BER) which targets erroneous bases in the DNA. Here, Uracil-DNA glycosylases (UDGs) are responsible for recognition and removal of uracil base from the DNA. Here, we characterize the interaction of Staphylococcus aureus UDG (SAUDG) with a naturally occurring variant of S. aureus uracil-DNA glycosylase inhibitor (SAUGI). This variant contains a histidine instead of a glutamate at the 24th position which affects the SAUDG:SAUGI interaction surface. We assessed the complex formation of SAUDG with these two SAUGI variants by independent biophysical methods. Our data reveal that the residue difference at the 24th position does not have a marked effect on the binding affinity, yet it confers alteration of the thermodynamics of the interaction. We propose that the E24H variant of SAUGI allows efficient complex formation, and consequently, inhibition of SAUDG. © 2018, Budapest University of Technology and Economics. All rights reserved.

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