Janssen Research used an integrative structural biology approach to study human malic enzyme 3 (ME3), a potential therapeutic target for pancreatic cancer.
A team from Janssen Research used an integrative structural biology approach to study human malic enzyme 3 (ME3), a potential therapeutic target for pancreatic cancers. Through a combination of crystallography and Cryo-EM, the team generated five distinct structures which improve our understanding of the conformation dynamics, flexibility, and potential regulation of the enzyme. ME3 proves to be a non-allosterically regulated enzyme with a highly flexible loop AB suggesting a distinct regulatory and functional role from other enzymes in the same family. The additional structural information may help to explain the specificity of therapeutics targeting malic enzymes and enable structure based drug design for ME3.
Tsehai A.J. Grell, Mark Mason, Aaron A. Thompson, Jose Carlos Gmez-Tamayo, Daniel Riley, Michelle V. Wagner, Ruth Steele, Rodrigo F. Ortiz-Meoz, Jay Wadia, Paul L. Shaffer, Gary Tresadern, Sujata Sharma, Xiaodi Yu, Integrative structural and functional analysis of human malic enzyme 3: A potential therapeutic target for pancreatic cancer, Heliyon, Volume 8, Issue 12, 2022; doi.org/10.1016/j.heliyon.2022.e12392
