BioDesign 2020; 8(1): 24-27
Published online March 30, 2020
© Korean Society for Structural Biology
Sang Hyung Lee, Hyun Tae Lee, Heejin Lim, Yujin Kim and Yong-Seok Heo*
Department of Chemistry, Konkuk University, Seoul 05029, Republic of Korea
Correspondence to: *email@example.com
Cardiovascular disease (CVD) is the leading cause of death globally and its major risk factor is cholesterol. Even though statins are often prescribed to lower blood levels of low-density lipoprotein cholesterol (LDL-C), not all the high-risk patients were able to achieve a targeted level of LDL-C. PCSK9 protein plays a major role in LDL receptor degradation and is a prominent modulator in LDL-C metabolism. Two monoclonal antibodies inhibiting PCSK9, evolocumab and alirocumab, are approved by the US FDA in 2015. Anti-PCSK9 antibody drugs could lead to a substantial decrement in LDL-C plasma level, either as a monotherapy or combination with statins. Moreover, PCSK9 inhibitors do not appear to increase the risk of hepatic and muscle-related side effects. Here, the Fab fragment of evolocumab was overexpressed, purified, and crystallized. The crystal diffracted to 2.00 Å resolution and belonged to the space group R32, with unit cell parameters a = b = 107.09, and c = 182.39 Å. An asymmetric unit of the crystal contains one Fab molecule of evolocumab with a VM of 2.32 Å3 Da-1 and a solvent content of 47.00%.