探究H-NOX家族中血红素畸变的功能。
Probing the function of heme distortion in the H-NOX family.
作者信息
Olea Charles, Boon Elizabeth M, Pellicena Patricia, Kuriyan John, Marletta Michael A
机构信息
Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, California 94720, USA.
出版信息
ACS Chem Biol. 2008 Nov 21;3(11):703-10. doi: 10.1021/cb800185h.
Hemoproteins carry out diverse functions utilizing a wide range of chemical reactivity while employing the same heme prosthetic group. It is clear from high-resolution crystal structures and biochemical studies that protein-bound hemes are not planar and adopt diverse conformations. The crystal structure of an H-NOX domain from Thermoanaerobacter tengcongensis (Tt H-NOX) contains the most distorted heme reported to date. In this study, Tt H-NOX was engineered to adopt a flatter heme by mutating proline 115, a conserved residue in the H-NOX family, to alanine. Decreasing heme distortion in Tt H-NOX increases affinity for oxygen and decreases the reduction potential of the heme iron. Additionally, flattening the heme is associated with significant shifts in the N-terminus of the protein. These results show a clear link between the heme conformation and Tt H-NOX structure and demonstrate that heme distortion is an important determinant for maintaining biochemical properties in H-NOX proteins.
血红素蛋白利用相同的血红素辅基，凭借广泛的化学反应性执行多种功能。从高分辨率晶体结构和生化研究中可以清楚地看到，与蛋白质结合的血红素并非平面结构，而是呈现出多种构象。嗜热栖热菌（Thermoanaerobacter tengcongensis）的H-NOX结构域（Tt H-NOX）的晶体结构包含了迄今为止报道的最扭曲的血红素。在本研究中，通过将H-NOX家族中的保守残基脯氨酸115突变为丙氨酸，对Tt H-NOX进行改造，使其血红素更扁平。降低Tt H-NOX中血红素的扭曲程度会增加其对氧气的亲和力，并降低血红素铁的还原电位。此外，使血红素变扁平与蛋白质N端的显著位移有关。这些结果表明血红素构象与Tt H-NOX结构之间存在明确的联系，并证明血红素扭曲是维持H-NOX蛋白生化特性的重要决定因素。
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