Crystal structure of MqnD (TTHA1568), a menaquinone biosynthetic enzyme from Thermus thermophilus HB8

Ryoichi Arai, Kazutaka Murayama, Tomomi Uchikubo-Kamo, Madoka Nishimoto, Mitsutoshi Toyama, Seiki Kuramitsu, Takaho Terada, Mikako Shirouzu, Shigeyuki Yokoyama

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10 Citations (Scopus)

Abstract

In many microorganisms, menaquinone is an essential lipid-soluble electron carrier. Recently, an alternative menaquinone biosynthetic pathway was found in some microorganisms [Hiratsuka, T., Furihata, K., Ishikawa, J., Yamashita, H., Itoh, N., Seto, H., Dairi, T., 2008. An alternative menaquinone biosynthetic pathway operating in microorganisms. Science 321, 1670-1673]. Here, we report the 1.55 Å crystal structure of MqnD (TTHA1568) from Thermus thermophilus HB8, an enzyme within the alternative menaquinone biosynthetic pathway. The structure comprises two domains with α/β structures, a large domain and a small domain. L(+)-Tartaric acid was bound to the pocket between the two domains, suggesting that this pocket is a putative active site. The conserved glycine residues at positions 78, 80 and 82 seem to act as hinges, allowing the substrate to access the pocket. Highly conserved residues, such as Asp14, Asp38, Asn43, Ser57, Thr107, Ile144, His145, Glu146, Leu176 and Tyr234, are located at this pocket, suggesting that these residues are involved in substrate binding and/or catalysis, and especially, His145 could function as a catalytic base. Since humans and their commensal intestinal bacteria, including lactobacilli, lack the alternative menaquinone biosynthetic pathway, this enzyme in pathogenic species, such as Helicobacter pylori and Campylobacter jejuni, is an attractive target for the development of chemotherapeutics. This high-resolution structure may contribute toward the development of its inhibitors.

Original languageEnglish
Pages (from-to)575-581
Number of pages7
JournalJournal of Structural Biology
Volume168
Issue number3
DOIs
Publication statusPublished - 2009 Dec

Keywords

  • Alternative menaquinone biosynthetic pathway
  • DUF191
  • Menaquinone
  • MqnD
  • Thermus thermophilus

ASJC Scopus subject areas

  • Structural Biology

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    Arai, R., Murayama, K., Uchikubo-Kamo, T., Nishimoto, M., Toyama, M., Kuramitsu, S., Terada, T., Shirouzu, M., & Yokoyama, S. (2009). Crystal structure of MqnD (TTHA1568), a menaquinone biosynthetic enzyme from Thermus thermophilus HB8. Journal of Structural Biology, 168(3), 575-581. https://doi.org/10.1016/j.jsb.2009.07.007