Yokoyama Takeshi, Neya Saburo, Tsuneshige Antonio, Yonetani Takashi, Park Sam-Yong, Tame Jeremy R H
Protein Design Laboratory, Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro, Tsurumi, Yokohama, 230-0045, Japan.
J Mol Biol. 2006 Feb 24;356(3):790-801. doi: 10.1016/j.jmb.2005.12.018. Epub 2005 Dec 21.
Although detailed crystal structures of haemoglobin (Hb) provide a clear understanding of the basic allosteric mechanism of the protein, and how this in turn controls oxygen affinity, recent experiments with artificial effector molecules have shown a far greater control of oxygen binding than with natural heterotropic effectors. Contrary to the established text-book view, these non-physiological compounds are able to reduce oxygen affinity very strongly without switching the protein to the T (tense) state. In an earlier paper we showed that bezafibrate (BZF) binds to a surface pocket on the alpha subunits of R state Hb, strongly reducing the oxygen affinity of this protein conformation. Here we report the crystallisation of Hb with L35, a related compound, and show that this binds to the central cavity of both R and T state Hb. The mechanism by which L35 reduces oxygen affinity is discussed, in relation to spectroscopic studies of effector binding.
尽管血红蛋白（Hb）的详细晶体结构能让人清楚了解该蛋白质的基本变构机制，以及这如何反过来控制氧亲和力，但最近使用人工效应分子的实验表明，与天然异促效应剂相比，对氧结合的控制要强得多。与既定的教科书观点相反，这些非生理性化合物能够非常强烈地降低氧亲和力，而不会将蛋白质转变为T（紧张）状态。在早期的一篇论文中，我们表明苯扎贝特（BZF）与R态Hb的α亚基上的一个表面口袋结合，强烈降低了这种蛋白质构象的氧亲和力。在此我们报告了Hb与相关化合物L35的结晶情况，并表明它与R态和T态Hb的中央腔都有结合。结合效应剂的光谱学研究，讨论了L35降低氧亲和力的机制。
