BioCentury
ARTICLE | Distillery Techniques

Techniques: Crystal structure of myeloid leukemia cell differentiation protein (MCL1)

June 18, 2015 7:00 AM UTC

Crystallographic studies on an MCL1 fusion protein could aid the structure-based design of MCL1-specific inhibitors. A fusion of maltose binding protein and MCL1 containing three mutations to enhance its crystal packing properties formed crystals on its own, and formed co-crystals with known MCL1 ligands, whereas unfused, wild-type MCL1 did not form crystals. For three known MCL1 ligands, Kd values for binding of each to the fusion protein and to unfused, wild-type MCL1 were comparable. In co-crystals of the MCL1 fusion protein with the three ligands and three fragment molecules, crystallographic analyses revealed multiple structural and atomic details about MCL1's binding interactions. Next steps could include using the MCL1 fusion protein in the design of potent, selective MCL1 inhibitors. (See "Watershed Crystal", page 16)

Teva Pharmaceutical Industries Ltd. and Hospira Inc. market Synribo omacetaxine mepesuccinate, a small molecule that inhibits synthesis of MCL1 and cyclin D1 (CCND1; BCL1), to treat chronic myelogenous leukemia (CML)...