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The role of Phe181 in the hexamerization of Helicobacter pylori quinolinate phosphoribosyltransferase.
Protein J. 2007 Oct; 26(7):517-21.PJ

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 alpha7 and strand beta8 contributes significantly to the hydrophobic dimer-dimer interactions. Phe181Pro mutation within the alpha7-beta8 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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Authors+Show Affiliations

Kim MK
Department of Life Science, Gwangju Institute of Science & Technology, Gwangju, 500-712, Republic of Korea.
Kang GB
No affiliation info available
Song WK
No affiliation info available
Eom SH
No affiliation info available

MeSH

Bacterial ProteinsBinding SitesDimerizationHelicobacter pyloriModels, MolecularPentosyltransferasesPhenylalaninePoint MutationProlineProtein Conformation

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17763926

Citation

Kim, M-K, et al. "The Role of Phe181 in the Hexamerization of Helicobacter Pylori Quinolinate Phosphoribosyltransferase." The Protein Journal, vol. 26, no. 7, 2007, pp. 517-21.
Kim MK, Kang GB, Song WK, et al. The role of Phe181 in the hexamerization of Helicobacter pylori quinolinate phosphoribosyltransferase. Protein J. 2007;26(7):517-21.
Kim, M. K., Kang, G. B., Song, W. K., & Eom, S. H. (2007). The role of Phe181 in the hexamerization of Helicobacter pylori quinolinate phosphoribosyltransferase. The Protein Journal, 26(7), 517-21.
Kim MK, et al. The Role of Phe181 in the Hexamerization of Helicobacter Pylori Quinolinate Phosphoribosyltransferase. Protein J. 2007;26(7):517-21. PubMed PMID: 17763926.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of Phe181 in the hexamerization of Helicobacter pylori quinolinate phosphoribosyltransferase. AU - Kim,M-K, AU - Kang,G B, AU - Song,W K, AU - Eom,S H, PY - 2007/9/4/pubmed PY - 2008/1/24/medline PY - 2007/9/4/entrez SP - 517 EP - 21 JF - The protein journal JO - Protein J VL - 26 IS - 7 N2 - 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 alpha7 and strand beta8 contributes significantly to the hydrophobic dimer-dimer interactions. Phe181Pro mutation within the alpha7-beta8 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. SN - 1572-3887 UR - https://www.unboundmedicine.com/medline/citation/17763926/The_role_of_Phe181_in_the_hexamerization_of_Helicobacter_pylori_quinolinate_phosphoribosyltransferase_ L2 - https://link.springer.com/article/10.1007/s10930-007-9093-0 DB - PRIME DP - Unbound Medicine ER -