Yang J, Kloek A P, Goldberg D E, Mathews F S
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4224-8. doi: 10.1073/pnas.92.10.4224.
The perienteric hemoglobin of the parasitic nematode Ascaris has an exceptionally high affinity for oxygen. It is an octameric protein containing two similar heme-binding domains per subunit, but recombinant constructs expressing a single, monomeric heme-binding domain (domain 1; D1) retain full oxygen avidity. We have solved the crystal structure of D1 at 2.2 A resolution. Analysis of the structure reveals a characteristic globin fold and illuminates molecular features involved in oxygen avidity of Ascaris perienteric hemoglobin. A strong hydrogen bond between tyrosine at position 10 in the B helix (tyrosine-B10) and the distal oxygen of the ligand, combined with a weak hydrogen bond between glutamine-E7 and the proximal oxygen, grips the ligand in the binding pocket. A third hydrogen bond between these two amino acids appears to stabilize the structure. The B helix of D1 is displaced laterally by 2.5 A when compared with sperm whale myoglobin. This shifts the tyrosine-B10 hydroxyl far enough from liganded oxygen to form a strong hydrogen bond without steric hindrance. Changes in the F helix compared with myoglobin contribute to a tilted heme that may also be important for oxygen affinity.
寄生线虫蛔虫的肠周血红蛋白对氧气具有极高的亲和力。它是一种八聚体蛋白，每个亚基包含两个相似的血红素结合结构域，但表达单个单体血红素结合结构域（结构域1；D1）的重组构建体仍保留完全的氧亲和力。我们已解析出D1在2.2埃分辨率下的晶体结构。对该结构的分析揭示了一种特征性的珠蛋白折叠，并阐明了与蛔虫肠周血红蛋白氧亲和力相关的分子特征。B螺旋中第10位的酪氨酸（酪氨酸-B10）与配体的远端氧之间存在强氢键，同时谷氨酰胺-E7与近端氧之间存在弱氢键，将配体固定在结合口袋中。这两个氨基酸之间的第三个氢键似乎稳定了结构。与抹香鲸肌红蛋白相比，D1的B螺旋横向位移了2.5埃。这使得酪氨酸-B10的羟基远离配位氧，足以形成强氢键而无空间位阻。与肌红蛋白相比，F螺旋的变化导致血红素倾斜，这可能对氧亲和力也很重要。
