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首页> 外文期刊>Biochemistry >Straight-Chain Alkyl Isocyanides Open the Distal Histidine Gate in Crystal Structures of Myoglobin,
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Straight-Chain Alkyl Isocyanides Open the Distal Histidine Gate in Crystal Structures of Myoglobin,

机译：直链烷基异氰酸酯在肌红蛋白的晶体结构中打开组氨酸的远端门，

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摘要

Crystal structures of methyl, ethyl, propyl, and butyl isocyanide bound to sperm whalemyoglobinn(Mb) reveal two major conformations. In the in conformer, His(E7) is in a “closed” position, forcing thenligand alkyl chain to point inward. In the out conformer, His(E7) is in an “open” position, allowing the ligandnside chain to point outward. A progressive increase in the population of the out conformer is observed withnincreasing ligand length in P21 crystals of native Mb at pH 7.0. This switch from in to out with increasingnligand size also occurs in solution as measured by the decrease in the relative intensity of the low-frequencyn(∼2075 cm-1n) versus high-frequency (∼2125 cm-1n) isocyano bands. In contrast, all four isocyanides in P6ncrystals of wild-type recombinant Mb occupy the in conformation. However, mutating either His64 to Ala,ncreating a “hole” to solvent, or Phe46 to Val, freeing rotation ofHis64, causes bound butyl isocyanide to pointncompletely outward in P6 crystals. Thus, the unfavorable hindrance caused with crowding a large alkyl sidenchain into the distal pocket appears to be roughly equal to that for pushing open theHis(E7) gate and is easilynaffected by crystal packing. This structural conclusion supports the “side path” kinetic mechanism for O2nrelease, in which the dissociated ligand first moves toward the protein interior and then encounters stericnresistance, which is roughly equal to that for escaping to solvent through the His(E7) channel.
机译：甲基，乙基，丙基和丁基异氰酸酯结合到精子鲸卵红蛋白（Mb）的晶体结构揭示了两个主要构象。在构象异构体中，His（E7）处于“闭合”位置，从而迫使配体烷基链向内指向。在外构象异构体中，His（E7）处于“开放”位置，使配体侧链指向外部。在pH 7.0下，天然Mb的P21晶体中随着配体长度的增加，观察到外构型群体的逐渐增加。随着配体尺寸的增加，这种从内到外的转换也发生在溶液中，这是通过测量低频n（〜2075 cm-1n）与高频（〜2125 cm-1n）异氰酸基带的相对强度降低来衡量的。相反，野生型重组Mb的P6n晶体中的所有四个异氰化物均占据该构象。但是，将His64突变为Ala，对溶剂产生一个“孔”，或者将Phe46突变为Val，释放His64的旋转，会导致结合的异氰酸丁基酯在P6晶体中完全指向外部。因此，由大的烷基侧链拥挤到远端袋中引起的不利障碍似乎与推开His（E7）门的障碍大致相等，并且很容易受到晶体堆积的影响。该结构性结论支持了O2n释放的“旁通路”动力学机制，其中解离的配体首先向蛋白质内部移动，然后遇到空间抗性，这大致等于通过His（E7）通道逃逸到溶剂中的空间抗性。

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  • 来源
    《Biochemistry》 |2010年第24期|p.4977-4986|共10页
  • 作者

    Robert D. Smith George C. Blouin Kenneth A. Johnson George N. Phillips Jr. and John S. Olson;

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    Department of Biochemistry and Cell Biology and W. M. Keck Center for Computational Biology, Rice University, Houston,Texas 77005, and Departments of Biochemistry and Computer Sciences, University of Wisconsin,Madison, Madison,Wisconsin 53706 §These authors provided equal contributions to this work ) Present address: Department of Emergency HealthSciences, University of Texas Health Science Center, San Antonio, TX ^Present address: Physics Laboratory,Biophysics Group, National Institute of Standards and Technology, Gaithersburg, MD #Present address: Department of Chemistry, Faculty of Sciences, University of Tromsø, Tromsø, Norway)Present address: Department of Biochemistry, University of Wisconsin, Madison, WI,;

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