Potential influence of Asp in the Ca2+ coordination position 5 of parvalbumin on the calcium-binding affinity: a computational study.
Potential influence of Asp in the Ca2+ coordination position 5 of parvalbumin on the calcium-binding affinity: a computational study.
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小清蛋白 Ca2 配位 5 中的天冬氨酸对钙结合亲和力的潜在影响：一项计算研究。
DOI：
10.1016/j.jinorgbio.2006.07.016
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发表时间：
2006
影响因子：
3.9
通讯作者：
Huo,Shuanghong
中科院分区：
文献类型：
--
作者：
Zhao,Jingyan;Nelson,DonaldJ;Huo,Shuanghong
小白蛋白（PV）是钙结合蛋白，它们都具有共同的螺旋-环-螺旋（EF-hand）基序。这个基序包含一个中央的12个残基Ca2+结合环，两侧的螺旋彼此大致垂直。这些配位残基的确切作用一直是激烈研究的主题。在这项工作中，我们重点研究了银鳕小蛋白异构体B (SHPV-B) CD Ca2+结合位点的配位5。典型ef -hand中钙结合环第5位最常见的残基是Asp [B.J.]马斯登，G.S.肖，B.D.赛克斯，生物化学。细胞生物学，68(1990)587-601]，但在PV的CD位点，这个位置几乎总是丝氨酸（Ser）。用Asp取代Ser会在CD配位球中增加第5个羧酸残基。然而，正如酸对假说所预测的那样，在具有四个羧酸配体沿±x和±z轴配对的EF-hand基序中，Ca2+结合亲和力将最大化里德，R.S.霍奇斯，J. Theor。生物学杂志。84(1980)401-444。采用分子动力学模拟和自由能计算研究了5位Ser - Asp突变对钙结合亲和力的影响。我们发现，在整个分子动力学模拟过程中，Asp变体表现出显著的稳定性，不仅保留了Ca2+结合位点，而且增加了配位球的紧密性。S55D片段也能很好地容纳Ca2+。我们得出结论，Asp是典型ef -hand中钙结合环第5位最常见的残基，但从未在pv的这个位置被实验发现，其原因可能与其生理功能有关。
Parvalbumins (PV) are calcium-binding proteins, all sharing the common helix–loop–helix (EF-hand) motif. This motif contains a central twelve-residue Ca2+-binding loop with the flanking helices positioned roughly perpendicular to each other. The precise role of these coordination residues has been the subject of intense studies. In this work, we focus on the coordination position 5 in the CD Ca2+-binding site of silver hake parvalbumin isoform B (SHPV-B). The most common residue at site 5 of calcium-binding loop in canonical EF-hands is Asp [B.J. Marsden, G.S. Shaw, B.D. Sykes, Biochem. Cell Biol. 68 (1990) 587–601], but in the CD site of PV, this position is almost always serine (Ser). The substitution of Ser with Asp will add the 5th carboxylate residue in the CD coordination sphere. However, as predicted by the acid pair hypothesis, the Ca2+-binding affinity would be maximized in an EF-hand motif that has four carboxylate ligands paired along the ±x, and ±z-axes [R.E. Reid, R.S. Hodges, J. Theor. Biol. 84 (1980) 401–444]. Molecular dynamics simulations and free energy calculations were employed to investigate the influence of Ser to Asp mutation at position 5 on calcium-binding affinity. We found that the Asp variant exhibited remarkable stability during the entire molecular dynamics simulation, with not only the retention of the Ca2+-binding site, but also increased compactness in the coordination sphere. The S55D fragment also accommodated Ca2+well. We conclude that the reason why Asp which is the most common residue at site 5 of calcium-binding loop in canonical EF-hands has never been identified at this position experimentally for PVs might be related to its physiological functions.