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BIO DESIGN

pISSN 2288-6982
eISSN 2288-7105

Article

Article

Crystallization

Bio Design 2020; 8(1): 24-27

Published online March 30, 2020

https://doi.org/10.34184/kssb.2020.8.1.24

© Korean Society for Structural Biology

Crystallization of the Fab fragment of evolocumab, an antibody-drug inhibiting PCSK9 for treating hypercholesterolemia

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: *ysheo@konkuk.ac.kr

Received: February 21, 2020; Revised: February 28, 2020; Accepted: March 5, 2020

Abstract

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%.