Hamelberg Donald, McCammon J Andrew
Howard Hughes Medical Institute, Center for Theoretical Biological Physics, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA.
J Am Chem Soc. 2005 Oct 12;127(40):13778-9. doi: 10.1021/ja054338a.
The catalytic aspartyl protease of the HIV-1 virus is a homodimer with two flaps that control access to the active site and are known to be flexible. However, knowledge of the atomistic mechanism of the flexibility is lacking. We show that the Gly-Gly omega-bond in the glycine-rich flap tips undergoes fast cis-trans isomerization on the microsecond to millisecond time scale rather than in the usual seconds. Further study reveals that the unexpectedly fast isomerization is a direct consequence of the beta-hairpin loop structure of the flap tips, which appears to be counterintuitive. After loop formation of a linear peptide containing the Gly-Gly motif, the rate of isomerization is shown to increase by many orders of magnitude.
人类免疫缺陷病毒1型（HIV-1）的催化天冬氨酰蛋白酶是一种同型二聚体，有两个控制活性位点通道的瓣片，已知其具有灵活性。然而，对于这种灵活性的原子机制却缺乏了解。我们发现，富含甘氨酸的瓣片尖端的甘氨酸-甘氨酸ω键在微秒到毫秒的时间尺度上发生快速顺反异构化，而不是通常的秒级时间尺度。进一步研究表明，这种意外的快速异构化是瓣片尖端β-发夹环结构的直接结果，这似乎有违直觉。在形成含有甘氨酸-甘氨酸基序的线性肽环后，异构化速率显示增加了多个数量级。
