pISSN 2288-6982
eISSN 2288-7105




BioDesign 2023; 11(4): 55-58

Published online December 30, 2023

© Korean Society for Structural Biology

Crystal structure of the Fab fragment of gemtuzumab ozogamicin, the first approved antibody-drug conjugate for induction therapy of AML

Seung Beom Choi, Yu-Jeong Jang, Nahyeon Gu and Yong-Seok Heo*

Department of Chemistry, Konkuk University, Seoul 05029, Republic of Korea

Correspondence to: *

Received: September 6, 2023; Revised: September 22, 2023; Accepted: September 22, 2023


Gemtuzumab ozogamicin is an antibody-drug conjugate consisting of a toxin chemically bound to an antibody that detects the CD33 protein on tumor cells. CD33 is a myeloid differentiation antigen displayed on acute myeloid leukemia (AML) blasts in most patients and has thus been highlighted as a potential target. When administrated to AML patients, gemtuzumab binds to CD33 and facilitates the uptake of the toxic payload into the cells, leading to cell death. Here, the crystal structure of the gemtuzumab Fab was determined to 2.50 Å resolution, with R/Rfree = 0.191/0.219. The five complementarity determining regions (CDRs) of gemtuzumab but the CDR1 of the heavy chain (HCDR1) are clearly displayed in the structure with apparent electron density. The results of this structural study may aid in predicting the binding mode of gemtuzumab to CD33, supporting the development of an ADC with increased therapeutic potency for the treatment of AML.