Crystal structure of the Fab fragment of burosumab, the first-in-class anti-FGF23 medicine for treating X-linked hypophosphatemia and tumor-induced osteomalacia

• 발행기관: 한국구조생물학회
• 저자명: Ui Beom Park Hyun Tae Lee Yujin Kim Tae Jun Jeong Nahyun Gu Yong-Seok Heo
• 간행물 정보: 『Biodesign』Vol 9, No 4, Dec, 59~62쪽, 전체 4쪽
• 주제분류: 자연과학 > 생물학
• 파일형태: PDF
• 발행일자: 2021.12.31

영문 초록

Burosumab is a first-in-class therapy approved to treat X-linked hypophosphatemia and tumor-induced osteomalacia, a condition associated with excessive fibroblast growth factor 23 (FGF23) production. This antibody drug directly targets the excessive FGF23 in patients and inhibits its regulation of phosphate homeostasis and vitamin D metabolism. Here, the Fab fragment of burosumab was expressed, purified, and crystallized. The crystals belonged to the space group P21, with unit cell parameters a = 49.51, b = 66.22, c = 62.05 Å, and β = 105.99°. An asymmetric unit of the crystal contains one Fab fragment with a Matthews coefficient of 1.93 Å3 Da-1. The structure was determined at a resolution of 1.45 Å, with Rwork/Rfree = 0.169/0.196. The complementarity determining regions of burosumab construct a negatively charged patch, a putative hot spot for FGF23 binding. This high-resolution structure could be used for predicting the binding mode between burosumab and FGF23.

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