Crystal Structure of HugZ, a Novel Heme Oxygenase from Helicobacter pylori
Crystal Structure of HugZ, a Novel Heme Oxygenase from Helicobacter pylori
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DOI：
10.1074/jbc.m110.172007
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发表时间：
2011-01-14
影响因子：
4.8
通讯作者：
Wang, Da-Cheng
中科院分区：
文献类型：
--
作者：
Hu, Yonglin;Jiang, Fan;Wang, Da-Cheng
来自幽门螺杆菌的血红素加氧酶（HO）HugZ与血红素复合的晶体结构已经在1.8埃分辨率下解析和细化。HugZ是H.幽门螺杆菌是人类胃肠道疾病的主要病原体。它是H.宿主中的幽门螺杆菌。在这里，我们报告说，HugZ是不同于所有其他特征的HO。它以二聚体的形式存在于溶液和晶体中，二聚体采用裂桶折叠，这种折叠常在FMN结合蛋白中发现，但在血红素蛋白中未观察到。血红素位于单体间的界面处，并被两个单体结合。当血红素铁存在于结晶条件下时，其由His（245）的侧链和叠氮分子配位。实验表明，参与叠氮化物结合的Arg（166）对于HugZ酶活性是必不可少的，而令人惊讶的是，His（245）不是，这意味着HugZ具有不同于其他HO的酶机制。叠氮化物的放置证实了所观察到的血红素降解反应的γ-内消旋特异性，与大多数已知的具有α-内消旋特异性的HO相反。我们通过序列和结构的比较表明，HugZ属于一个新的血红素结合蛋白家族的分裂桶折叠。该家族的成员广泛存在于致病菌中，并可能在这些细菌的铁获取中发挥重要作用。
The crystal structure of a heme oxygenase (HO) HugZ from Helicobacter pylori complexed with heme has been solved and refined at 1.8 angstrom 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 His(245) 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 His(245), surprisingly, is not, implying that HugZ has an enzymatic mechanism distinct from other HOs. The placement of the azide corroborates the observed gamma-meso specificity for the heme degradation reaction, in contrast to most known HOs that have alpha-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.