Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation.
Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation.
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DOI：
10.1186/1472-6807-12-23
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发表时间：
2012-09-26
影响因子：
--
通讯作者：
Gu L
中科院分区：
文献类型：
--
作者：
Liu X;Gong J;Wei T;Wang Z;Du Q;Zhu D;Huang Y;Xu S;Gu L
HUTZ是在霍乱弧菌中发现的唯一的血红素储存蛋白，是最佳利用血红素所必需的。然而，没有观察到该蛋白的血红素加氧酶活性。到目前为止，Hutz的结构和血红素结合机制尚不清楚。我们首次报道了同源二聚体中Hutz的晶体结构，其分辨率为2.0。赫兹构造采用典型的裂桶褶皱。通过对接研究和定点突变，提出了Hutz二聚体的血红素结合模型。非常有趣的是，HUTZ与其同源蛋白HUGZ(幽门螺杆菌的一种血红素加氧酶)的结构重叠显示，HUTZ的β6中有一个氨基酸残基的结构不匹配，尽管这一区域的残基在两种蛋白质中都高度保守。不同单点变异的同源模型和模型评估表明，HutZ的Pro140对应于HugZ的Phe215，可能是导致结构错配的主要因素。这种错配导致它们的C-末端区域具有更多不同的结构特征，这是HugZ作为血红素加氧酶与血红素结合的基本特征。Hutz的血红素加氧酶活性不足可能源于其相对于血红素加氧酶HugZ的残基移动。这种残基移动也强调了同源建模的传统模板选择标准的局限性。
HutZ is the sole heme storage protein identified in the pathogenic bacterium Vibrio cholerae and is required for optimal heme utilization. However, no heme oxygenase activity has been observed with this protein. Thus far, HutZ’s structure and heme-binding mechanism are unknown. We report the first crystal structure of HutZ in a homodimer determined at 2.0 Å resolution. The HutZ structure adopted a typical split-barrel fold. Through a docking study and site-directed mutagenesis, a heme-binding model for the HutZ dimer is proposed. Very interestingly, structural superimposition of HutZ and its homologous protein HugZ, a heme oxygenase from Helicobacter pylori, exhibited a structural mismatch of one amino acid residue in β6 of HutZ, although residues involved in this region are highly conserved in both proteins. Derived homologous models of different single point variants with model evaluations suggested that Pro140 of HutZ, corresponding to Phe215 of HugZ, might have been the main contributor to the structural mismatch. This mismatch initiates more divergent structural characteristics towards their C-terminal regions, which are essential features for the heme-binding of HugZ as a heme oxygenase. HutZ’s deficiency in heme oxygenase activity might derive from its residue shift relative to the heme oxygenase HugZ. This residue shift also emphasized a limitation of the traditional template selection criterion for homology modeling.
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