The enigma of the liganded hemoglobin end state: A novel quaternary structure of human carbonmonoxy hemoglobin
The enigma of the liganded hemoglobin end state: A novel quaternary structure of human carbonmonoxy hemoglobin
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DOI：
10.1021/bi050412q
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发表时间：
2005-06-14
期刊：
影响因子：
2.9
通讯作者：
Abraham, DJ
中科院分区：
文献类型：
--
作者：
Safo, MK;Abraham, DJ
马克斯·佩鲁茨（Max Perutz）描述的配体血红蛋白（Hb）高盐结晶条件产生了三种不同的成人一氧化碳血红蛋白（COHbA）晶体。第一个晶体是同晶的“经典”配体或R Hb结构。第二种晶体揭示了一种新的配体Hb四级结构RR 2，它假定了R型和十多年前发现的另一种配体Hb四级结构R2之间的中间构象。与R2结构一样，RR 2结构中β 2 His 97和α 1 Thr 38之间的诊断性R状态氢键缺失。第三种晶体采用了一种新的配体Hb构象，我们称之为R3，它显示出与R，RR 2和R2结构的实质性四级结构差异。T和R3之间的四级结构差异与T和R2之间的四级结构差异一样大;然而，T -> R3和T -> R2转变是在由刚体螺旋旋转定义的不同方向上。此外，R3表示最终状态。与所有已知的配体Hb结构相比，R3显示出在α-血红素处显著降低的应变、β-血红素配体与远端残基之间降低的空间接触、较小的α-和β-裂缝以及降低的α 1-α 2和β 1-β 2铁-铁距离。总之，R3中的这些独特结构特征应使其与其他配体化Hb相比最松弛和/或大大增强其对氧的亲和力。目前基于T -> R、T R -> R2或T -> R2 -> R转换的Hb结构-功能关系可能必须重新检查，以考虑RR 2和R3配体结构。
The liganded hemoglobin (Hb) high-salt crystallization condition described by Max Perutz has generated three different crystals of human adult carbonmonoxy hemoglobin (COHbA). The first crystal is isomorphous with the "classical" liganded or R Hb structure. The second crystal reveals a new liganded Hb quaternary structure, RR2, that assumes an intermediate conformation between the R form and another liganded Hb quaternary structure, R2, which was discovered more than a decade ago. Like the R2 structure, the diagnostic R state hydrogen bond between beta 2His97 and alpha 1Thr38 is missing in the RR2 structure. The third crystal adopts a novel liganded Hb conformation, which we have termed R3, and it shows substantial quaternary structural differences from the R, RR2, and R2 structures. The quaternary structure differences between T and R3 are as large as those between T and R2; however, the T -> R3 and T -> R2 transitions are in different directions as defined by rigid-body screw rotation. Moreover, R3 represents an end state. Compared to all known liganded Hb structures, R3 shows remarkably reduced strain at the alpha-heme, reduced steric contact between the beta-heme ligand and the distal residues, smaller alpha-and beta-clefts, and reduced alpha 1-alpha 2 and beta 1-beta 2 iron-iron distances. Together, these unique structural features in R3 should make it the most relaxed and/or greatly enhance its affinity for oxygen compared to the other liganded Hbs. The current Hb structure -function relationships that are now based on T -> R, T R -> R2, or T -> R2 -> R transitions may have to be reexamined to take into account the RR2 and R3 liganded structures.