Structures of R- and T-state hemoglobin Bassett: elucidating the structural basis for the low oxygen affinity of a mutant hemoglobin.
Structures of R- and T-state hemoglobin Bassett: elucidating the structural basis for the low oxygen affinity of a mutant hemoglobin.
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R 态和 T 态血红蛋白的结构 Bassett：阐明突变血红蛋白的低氧亲和力的结构基础。
DOI：
10.1107/s0907444904030501
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Abraham,DonaldJ
中科院分区：
文献类型：
--
作者：
Safo,MartinK;Abdulmalik,Osheiza;Lin,HsiangRu;Asakura,Toshio;Abraham,DonaldJ
测定了R态和T态血红蛋白(HB)Bassett的晶体结构，其分辨率分别为2.15和1.80 。Hb Bassett(αAsp94→Ala)的生理特点是对氧的亲和力低，玻尔效应减弱，协作性低，并且略有不稳定(与正常成人血红蛋白相比；HbA)。将HB Bassett结构与先前确定的R态和T态HBA结构进行比较，发现该突变体具有与其他Hb相似的三级和四级结构。然而，这一分析确实发现了R态HbBassett和R态Hba在α1β2(α2β1)二聚体界面和β-Cleft上的局部结构差异。具体地说，在突变的R结构中，β-FG的拐角已经靠近α-C螺旋。此外，在天然R态Hb结构的α1β2界面上发现的4个亚基间氢键被取消或减弱，随后被R态Hb Bassett中的2个新的亚基间氢键所取代。值得注意的是，R态突变结构中新形成的氢键也在T态Hb结构中观察到。在β-Cleft，已知对Hb中的玻尔效应有贡献的βHis46与R态Hb Bassett中的βAsn139进行了独特的氢键相互作用。与R状态突变体不同，T状态HB Bassett结构在α1β2(α2β1)二聚体界面和β-Cleft上都没有显示出任何显著的结构变化。值得注意的是，该突变导致了涉及α1Asp94和β2Asp99的中间二聚体排斥力的去除。HB Bassett的R-态和T-态结构表明，该突变体的功能特性具有立体化学基础。
The crystal structures of R- and T-state hemoglobin (Hb) Bassett have been determined to 2.15 and 1.80 Å resolution, respectively. Physiologically, Hb Bassett (αAsp94→Ala) is characterized by a low affinity for oxygen, a reduced Bohr effect and low cooperativity, as well as being slightly unstable (compared with normal adult hemoglobin; HbA). Comparisons between the Hb Bassett structures and previously determined R- and T-state HbA structures revealed that this mutant shares similar tertiary and quaternary structures with other Hbs. However, this analysis did identify localized structural differences between R-state Hb Bassett and R-state HbA at the α1β2 (α2β1) dimer interface and at the β-cleft. Specifically, the β-FG corner has shifted closer to the α-C helix in the mutant R structure. In addition, four intersubunit hydrogen bonds found at the α1β2 interfaces of native R-state Hb structures are abolished or weakened and subsequently replaced by two new intersubunit hydrogen bonds in R-state Hb Bassett. Remarkably, the newly formed hydrogen bonds in the R-state mutant structure are also observed in T-state Hb structures. At the β-cleft, βHis46, which is known to contribute to the Bohr effect in Hb, makes a unique hydrogen-bonding interaction with βAsn139 in the R-state Hb Bassett. Unlike the R-state mutant, the T-state Hb Bassett structure does not display any significant structural changes at both the α1β2 (α2β1) dimer interface and the β-cleft. Quite significantly, the mutation has led to removal of an interdimer repulsion involving α1Asp94 and β2Asp99. The R- and T-state structures of Hb Bassett suggest a stereochemical basis for the observed functional properties of this mutant.