A dramatic conformational rearrangement is necessary for the activation of DNR from Pseudamanas aeruginosa. Crystal structure of wild-type DNR
A dramatic conformational rearrangement is necessary for the activation of DNR from Pseudamanas aeruginosa. Crystal structure of wild-type DNR
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DOI：
10.1002/prot.22428
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发表时间：
2009-10-01
影响因子：
2.9
通讯作者：
Cutruzzola, Francesca
中科院分区：
文献类型：
--
作者：
Giardina, Giorgio;Rinaldo, Serena;Cutruzzola, Francesca
条件致病菌铜绿假单胞菌可以在低氧条件下生长，因为它能够利用硝酸盐作为末端电子受体进行无氧呼吸（反硝化）。脱氮途径的中间体是一氧化氮，一种在高浓度下可能具有细胞毒性的化合物。一氧化氮的细胞内水平通过调节负责其合成和降解的酶（亚硝酸盐和一氧化氮还原酶）的表达来严格控制。在这篇文章中，我们提出了野生型异化硝酸盐呼吸调节剂（DNR）的晶体结构，一个主调节器控制反硝化机制的表达和新的治疗策略的推定目标。与CRP-FNR类调节剂中的其他结构的比较揭示了DNR以以前从未观察到的构象结晶。特别地，DNR的感测域相对于其他结构经历了超过50度的旋转。这表明DNR在活化时可能发生意想不到的和非常大的构象重排。
The opportunistic pathogen Pseudomonas aeruginosa can grow in low oxygen, because it is capable of anaerobic respiration using nitrate as a terminal electron acceptor (denitrification). An intermediate of the denitrification pathway is nitric oxide, a compound that may become cytotoxic at high concentration. The intracellular levels of nitric oxide are tightly controlled by regulating the expression of the enzymes responsible for its synthesis and degradation (nitrite and nitric oxide reductases). In this article, we present the crystallographic structure of the wild-type dissimilative nitrate respiration regulator (DNR), a master regulator controlling expression of the denitrification machinery and a putative target for new therapeutic strategies. Comparison with other structures among the CRP-FNR class Of regulators reveals that DNR has crystallized in a conformation that has never been observed before. In particular, the sensing domain of DNR has undergone a rotation of more than 50 degrees with respect to the other structures. This suggests that DNR may undergo an unexpected and very large conformational rearrangement on activation.