Koyama S, Kobayashi Y, Ohkubo T, Kyogoku Y, Sato A, Kobayashi M, Go N
Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Protein Eng. 1990 Apr;3(5):393-402. doi: 10.1093/protein/3.5.393.
The differences in conformation between alpha-human atrial natriuretic polypeptide (alpha-hANP) and its inactive analog, Met(O)-alpha-hANP, have been analyzed by nuclear magnetic resonance spectroscopy. All proton resonances for both peptides were assigned by means of the sequential assignment procedure. The three-dimensional structure of alpha-hANP in solution had previously been determined by distance geometry calculation using distance constraints derived from nuclear Overhauser effects (NOEs). Here, the three-dimensional structure of Met(O)-alpha-hANP was determined. The conformational differences between these two molecules were as follows: three segments of alpha-hANP, Ser1-Cys7, Arg11-Ala17 and Gln18-Tyr28, have some ordered structures. In Met(O)-alpha-hANP the Gln18-Tyr28 region has a similar conformation, while the remaining two regions do not have the ordered structure found in alpha-hANP. It is suggested that the conserved conformation of the Gln18-Tyr28 region is required for binding to the ANP receptor and that the slight biological activity of Met(O)-alpha-hANP is due to loss of the ordered structures evoked in the Ser1-Cys7 and Arg11-Ala17 regions of alpha-hANP.
已通过核磁共振光谱分析了α-人心房利钠多肽（α-hANP）与其无活性类似物Met（O）-α-hANP之间的构象差异。借助序列归属程序对两种肽的所有质子共振进行了归属。溶液中α-hANP的三维结构先前已通过使用源自核Overhauser效应（NOE）的距离约束进行距离几何计算来确定。在此，确定了Met（O）-α-hANP的三维结构。这两种分子之间的构象差异如下：α-hANP的三个片段，即Ser1-Cys7、Arg11-Ala17和Gln18-Tyr28，具有一些有序结构。在Met（O）-α-hANP中，Gln18-Tyr28区域具有相似的构象，而其余两个区域没有在α-hANP中发现的有序结构。有人提出，Gln18-Tyr28区域的保守构象是与ANP受体结合所必需的，并且Met（O）-α-hANP的轻微生物活性是由于α-hANP的Ser1-Cys7和Arg11-Ala17区域中诱发的有序结构的丧失。
