Spectroscopic characterization of the soluble guanylate cyclase-like heme domains from Vibrio cholerae and Thermoanaerobacter tengcongensis
Spectroscopic characterization of the soluble guanylate cyclase-like heme domains from Vibrio cholerae and Thermoanaerobacter tengcongensis
复制标题
DOI：
10.1021/bi049374l
复制
发表时间：
2004-08-10
期刊：
影响因子：
2.9
通讯作者：
Marletta, MA
中科院分区：
文献类型：
--
作者：
Karow, DS;Pan, DH;Marletta, MA
可溶性鸟苷酸环化酶（sGC）是一种一氧化氮（NO-）敏感血红素蛋白，已在从果蝇到人类的真核生物中发现。最近通过基因组分析鉴定了与sGC的血红素结构域具有显著同源性的前体蛋白。本文报道了其中两种蛋白质的特性。第一个是从霍乱弧菌（VCA 0720）克隆的181个氨基酸的蛋白质，其编码在含组氨酸激酶的操纵子中。VCA 0720的亚铁未连接形式是5配位、高自旋。CO络合物是低自旋的，6-配位的，而NO络合物是高自旋的，5-配位的。这些配体结合性质与sGC的那些非常相似。第二个蛋白质是Tar 4（TtTar 4 H）的N-末端188个氨基酸，Tar 4是来自严格厌氧菌Thermoanaerobactertengcongensis的预测的甲基接受趋化蛋白（MCP）。TtTar 4 H形成低自旋、6配位的亚铁-氧复合物，这是结合O-2的sGC相关家族中的第一个。TtTar 4 H具有与含血红素的O-2传感器如AxPDEA 1类似的配体结合特性。sGC不结合O-2，尽管具有像球蛋白那样的具有组氨酰配体的卟啉。这里报道的结果，与序列相关的蛋白质从原核生物，但在同一个家庭的sGC血红素域，表明这些蛋白质已经进化到区分配体，如NO和O-2，因此，我们这个家庭的H-NOX域（血红素-一氧化氮/氧）。
Soluble guanylate cyclase (sGC) is a nitric oxide- (NO-) sensing hemoprotein that has been found in eukaryotes from Drosophila to humans. Prokaryotic proteins with significant homology to the heme domain of sGC have recently been identified through genomic analysis. Characterization of two of these proteins is reported here. The first is a 181 amino acid protein cloned from Vibrio cholerae (VCA0720) that is encoded in a histidine kinase-containing operon. The ferrous unligated form of VCA0720 is 5-coordinate, high-spin. The CO complex is low-spin, 6-coordinate, and the NO complex is high-spin and 5-coordinate. These ligand-binding properties are very similar to those of sGC. The second protein is the N-terminal 188 amino acids of Tar4 (TtTar4H), a predicted methyl-accepting chemotaxis protein (MCP) from the strict anaerobe Thermoanaerobacter tengcongensis. TtTar4H forms a low-spin, 6-coordinate ferrous-oxy complex, the first of this sGC-related family that binds O-2. TtTar4H has ligand-binding properties similar to those of the heme-containing O-2 sensors such as AxPDEA1. sGC does not bind O-2 despite having a porphyrin with a histidyl ligand like the globins. The results reported here, with sequence-related proteins from prokaryotes but in the same family as the sGC heme domain, show that these proteins have evolved to discriminate between ligands such as NO and O-2; hence, we term this family H-NOX domains (heme-nitric oxide/oxygen).