Department of Chemistry, Georgetown University, Washington, DC 20057, USA.
Department of Chemistry/Industrial Biotechnology, P.O. Box 9000, University of Puerto Rico, Mayagüez Campus, 00681, Puerto Rico.
J Inorg Biochem. 2021 Nov;224:111578. doi: 10.1016/j.jinorgbio.2021.111578. Epub 2021 Aug 17.
The studies on the L. pectinata hemoglobins (HbI, HbII, and HbIII) are essential because of their biological roles in hydrogen sulfide transport and metabolism. Variation in the pH could also play a role in the transport of hydrogen sulfide by HbI and oxygen by HbII and HbIII, respectively. Here, fluoride binding was used to further understand the structural properties essential for the molecular mechanism of ligand stabilization as a function of pH. The data allowed us to gain insights into how the physiological roles of HbI, HbII, HbIII, adult hemoglobin (A-Hb), and horse heart myoglobin (Mb) have an impact on the heme-bound fluoride stabilization. In addition, analysis of the vibrational assignments of the met-cyano heme complexes shows varied strength interactions of the heme-bound ligand. The heme pocket composition properties differ between HbI (GlnE7 and PheB10) and HbII/HbIII (GlnE7 and TyrB10). Also, the structural GlnE7 stereo orientation changes between HbI and HbII/HbIII. In HbI, its carbonyl group orients towards the heme iron, while in HbII/HbIII, the amino group occupies this position. Therefore, in HbI, the interactions to the heme-bound fluoride ion, cyanide, and oxygen with GlnE7 via H-bonding are not probable. Still, the aromatic cage PheB10, PheCD1, and PheE11 may contribute to the observed stabilization. However, a robust H-bonding networking stabilizes HbII and HbIII, heme-bound fluoride, cyanide, and oxygen ligand with the OH and NH groups of TyrB10 and GlnE7, respectively. At the same time, A-Hb and Mb have moderate but similar ligand interactions controlled by their respective distal E7 histidine.
对 L. pectinata 血红蛋白（HbI、HbII 和 HbIII）的研究至关重要，因为它们在硫化氢的运输和代谢中具有生物学作用。pH 值的变化也可能分别在 HbI 运输硫化氢和 HbII 和 HbIII 运输氧中起作用。在这里，使用氟化物结合来进一步了解对配体稳定的分子机制至关重要的结构特性，作为 pH 的函数。该数据使我们能够深入了解 HbI、HbII、HbIII、成人血红蛋白（A-Hb）和马心肌红蛋白（Mb）的生理作用如何影响血红素结合氟化物的稳定。此外，对 met-cyano 血红素配合物的振动分配的分析表明，血红素结合配体的相互作用强度不同。血红素口袋组成特性在 HbI（GlnE7 和 PheB10）和 HbII/HbIII（GlnE7 和 TyrB10）之间有所不同。此外，结构 GlnE7 立体取向在 HbI 和 HbII/HbIII 之间发生变化。在 HbI 中，其羰基基团朝向血红素铁，而在 HbII/HbIII 中，氨基基团占据该位置。因此，在 HbI 中，通过氢键与 GlnE7 相互作用的血红素结合氟离子、氰化物和氧不太可能发生。尽管如此，芳香笼 PheB10、PheCD1 和 PheE11 可能有助于观察到的稳定化。然而，强的氢键网络稳定 HbII 和 HbIII，血红素结合的氟化物、氰化物和氧配体与 TyrB10 和 GlnE7 的 OH 和 NH 基团分别结合。同时，A-Hb 和 Mb 具有适度但相似的配体相互作用，由其各自的远端 E7 组氨酸控制。
