Janssen Research Uses an Integrative Structural Biology Approach to Generate Five Distinct Structures

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.