Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697-3900, United States; Department of Pharmaceutical Science, University of California, Irvine, CA 92697-3900, United States; Department of Chemistry, University of California, Irvine, CA 92697-3900, United States.
J Inorg Biochem. 2013 Nov;128:131-6. doi: 10.1016/j.jinorgbio.2013.07.030. Epub 2013 Jul 27.
Iron is an essential element to all living organisms and is an important determinant of bacterial virulence. Bacteria have evolved specialized systems to sequester and transport iron from the environment or host. Pseudomonas aeruginosa, an opportunistic pathogen, uses two outer membrane receptor mediated systems (Phu and Has) to utilize host heme as a source of iron. PhuS is a 39 kDa soluble cytoplasmic heme binding protein which interacts and transports heme from the inner membrane heme transporter to the cytoplasm where it is degraded by heme oxygenase thus releasing iron. PhuS is unique among other cytoplasmic heme transporter proteins owing to the presence of three histidines in the heme binding pocket which can potentially serve as heme ligands. Out of the three histidine residues on the heme binding helix, His 209 is conserved among heme trafficking proteins while His 210 and His 212 are unique to PhuS. Here we report the crystal structure of PhuS at 1.98Å resolution which shows a unique heme binding pocket and oligomeric structure compared to other known cytoplasmic heme transporter and accounts for some of the unusual biochemical properties of PhuS.
铁是所有生物的必需元素，也是细菌毒力的重要决定因素。细菌已经进化出专门的系统来从环境或宿主中隔离和运输铁。铜绿假单胞菌是一种机会性病原体，它使用两种外膜受体介导的系统（Phu 和 Has）利用宿主血红素作为铁源。PhuS 是一种 39 kDa 的可溶性细胞质血红素结合蛋白，它与血红素从内膜血红素转运蛋白相互作用并将其转运至细胞质，在细胞质中被血红素加氧酶降解，从而释放铁。PhuS 在其他细胞质血红素转运蛋白中是独特的，因为在血红素结合口袋中有三个组氨酸，它们可能作为血红素配体。在血红素结合螺旋上的三个组氨酸残基中，His209 在血红素转运蛋白中是保守的，而 His210 和 His212 是 PhuS 所特有的。在这里，我们报告了 PhuS 的晶体结构，分辨率为 1.98Å，与其他已知的细胞质血红素转运蛋白相比，它显示出独特的血红素结合口袋和寡聚结构，并解释了 PhuS 的一些不寻常的生化特性。
