PDF(Pubmed)
Abstract：
Due to the low temperature, the Antarctic marine environment is challenging for protein functioning. Cold-adapted organisms have evolved proteins endowed with higher flexibility and lower stability in comparison to their thermophilic homologs, resulting in enhanced reaction rates at low temperatures. The Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) genome is one of the few examples of coexistence of multiple hemoglobin genes encoding, among others, two constitutively transcribed 2/2 hemoglobins (2/2Hbs), also named truncated Hbs (TrHbs), belonging to the Group II (or O), annotated as PSHAa0030 and PSHAa2217. In this work, we describe the ligand binding kinetics and their interrelationship with the dynamical properties of globin Ph-2/2HbO-2217 by combining experimental and computational approaches and implementing a new computational method to retrieve information from molecular dynamic trajectories. We show that our approach allows us to identify docking sites within the protein matrix that are potentially able to transiently accommodate ligands and migration pathways connecting them. Consistently with ligand rebinding studies, our modeling suggests that the distal heme pocket is connected to the solvent through a low energy barrier, while inner cavities play only a minor role in modulating rebinding kinetics.
摘要：
由于温度低,南极海洋环境对蛋白质功能具有挑战性。与它们的嗜热同源物相比，适应冷的生物已经进化出具有更高的灵活性和更低的稳定性的蛋白质，导致在低温下提高反应速率。南极细菌雷单胞菌雷浮游假单胞菌TAC125（PhTAC125）基因组是编码多个血红蛋白基因共存的少数例子之一，其中,两个组成转录的2/2血红蛋白（2/2Hbs），也称为截断Hbs(TrHbs)，属于第二组(或O)，注释为PSHAa0030和PSHAa2217。在这项工作中,我们通过结合实验和计算方法，并实施一种新的计算方法从分子动力学轨迹中检索信息，描述了配体结合动力学及其与珠蛋白Ph-2/2HbO-2217动力学性质的相互关系。我们表明，我们的方法使我们能够识别蛋白质基质内的对接位点，这些对接位点可能能够暂时适应配体和连接它们的迁移途径。与配体再结合研究一致，我们的建模表明远端血红素口袋通过低能势垒连接到溶剂，而内腔在调节再结合动力学中只起次要作用。
