垂体牛生长激素组氨酸残基的质子核磁共振研究

Proton nuclear magnetic resonance study of the histidine residues of pituitary bovine growth hormone.

作者信息

MacKenzie N E, Plaisted S M, Brems D N

机构信息

Department of Pharmaceutical Sciences, University of Arizona, Tucson.

出版信息

Biochim Biophys Acta. 1989 Feb 2;994(2):166-71. doi: 10.1016/0167-4838(89)90156-8.

DOI:10.1016/0167-4838(89)90156-8

PMID:2910348

Abstract

The pKa value of histidines 20, 22 and 170 of pituitary bovine growth hormone (pbGH) and their C2H deuterium exchange rates have been determined by high-resolution 1H-NMR spectroscopy. Partial assignment of these parameters indicate that His-170 is a surface residue with a half-life for deuterium exchange at the C2H position of approx. 36 h and a pKa value of 5.68 +/- 0.11. A reversible conformational change of pbGH has also been characterized in terms of the involvement of either histidines 20 or 22. At or near physiological pH values, one of these residues is expelled from a buried, hydrophobic position to become fully solvent-exposed. The disparity in pKa values between histidines 20 and 22 (4.67 +/- 0.20 and 5.94 +/- 0.10, in some combination) has been shown by computer modeling, to be compatible with these residues residing in an alpha-helical region of the protein.

摘要

通过高分辨率1H-NMR光谱法测定了垂体牛生长激素（pbGH）的组氨酸20、22和170的pKa值及其C2H氘交换率。这些参数的部分归属表明，His-170是一个表面残基，其在C2H位置的氘交换半衰期约为36小时，pKa值为5.68±0.11。还根据组氨酸20或22的参与情况对pbGH的可逆构象变化进行了表征。在生理pH值或接近生理pH值时，这些残基中的一个从埋入的疏水位置被排出，从而完全暴露于溶剂中。计算机模拟显示，组氨酸20和22之间的pKa值差异（在某些组合中为4.67±0.20和5.94±0.10）与这些残基位于蛋白质的α-螺旋区域相一致。