The Role of Phe181 in the Hexamerization of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Quinolinate Phosphoribosyltransferase |
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Authors: | M-K Kim G B Kang W K Song S H Eom |
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Institution: | (1) Department of Life Science, Gwangju Institute of Science & Technology, Gwangju, 500-712, Republic of Korea |
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Abstract: | Quinolinic acid phosphoribosyltransferase (QAPRTase; NadC) catalyzes an indispensable step in NAD biosynthesis, one that is
essential for cell survival in prokaryotes, which makes it an attractive target for antibacterial drug therapy. We recently
reported the crystal structures of Helicobacter pylori QAPRTase with bound quinolinic acid, nicotinamide mononucleotide, and phthalic acid. The enzyme exists as a hexamer organized
as a trimer of dimers, which is essential for full enzymatic activity. The loop between helix α7 and strand β8 contributes
significantly to the hydrophobic dimer-dimer interactions. Phe181Pro mutation within the α7-β8 loop disrupts the hexamerization
of QAPRTase, and the resultant dimer shows dramatically reduced protein stability and no activity. Our findings thus suggest
that compounds able to disrupt its proper oligomerization could potentially function as selective inhibitors of Helicobacter pylori QAPRTase and represent a novel set of antibacterial agents. |
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Keywords: | Quinolinate phosphoribosyltransferase Hexamerization Drug target Helicobacter pylori |
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