Crystal structure of HugZ, a novel heme oxygenase from Helicobacter pylori

Yonglin Hu, Fan Jiang, Ying Guo, Xihui Shen, Ying Zhang, Rui Zhang, Gang Guo, Xuhu Mao, Quanming Zou, Da Cheng Wang

    Research output: Contribution to journalArticle

    25 Scopus citations

    Abstract

    The crystal structure of a heme oxygenase (HO) HugZ from Helicobacter pylori complexed with heme has been solved and refined at 1.8 Å resolution. HugZ is part of the iron acquisition mechanism of H. pylori, a major pathogen of human gastroenteric diseases. It is required for the adaptive colonization of H. pylori in hosts. Here, we report that HugZ is distinct from all other characterized HOs. It exists as a dimer in solution and in crystals, and the dimer adopts a split-barrel fold that is often found in FMN-binding proteins but has not been observed in hemoproteins. The heme is located at the intermonomer interface and is bound by both monomers. The heme iron is coordinated by the side chain of His245 and an azide molecule when it is present in crystallization conditions. Experiments show that Arg 166, which is involved in azide binding, is essential for HugZ enzymatic activity, whereas His245, surprisingly, is not, implying that HugZ has an enzymatic mechanism distinct from other HOs. The placement of the azide corroborates the observed γ-meso specificity for the heme degradation reaction, in contrast to most known HOs that have α-meso specificity. We demonstrate through sequence and structural comparisons that HugZ belongs to a new heme-binding protein family with a split-barrel fold. Members of this family are widespread in pathogenic bacteria and may play important roles in the iron acquisition of these bacteria.

    Original languageEnglish (US)
    Pages (from-to)1537-1544
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume286
    Issue number2
    DOIs
    StatePublished - Jan 14 2011

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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  • Cite this

    Hu, Y., Jiang, F., Guo, Y., Shen, X., Zhang, Y., Zhang, R., Guo, G., Mao, X., Zou, Q., & Wang, D. C. (2011). Crystal structure of HugZ, a novel heme oxygenase from Helicobacter pylori. Journal of Biological Chemistry, 286(2), 1537-1544. https://doi.org/10.1074/jbc.M110.172007