Crystal structure of monoacylglycerol lipase (MGLL)

US8080400B2 · kind B2 · utility

Assignee

• Janssen Pharmaceutica NA · BE

Inventors

• Carsten Schubert · Phoenixville, US
• Bruce Grasberger · Trappe, US
• Celine Schalk-Hihi · Phoenixville, US
• Diane M. Maguire · Downingtown, US
• Frank A. Lewandowski · Philadelphia, US
• Cynthia M. Milligan · Rutledge, US
• Richard S. Alexander · Newark, US

Key dates

• Filing date: Apr 24, 2009
• Grant date: Dec 20, 2011
• Expiry date: Apr 24, 2029

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2333/918
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

A number of soluble engineered forms of MGLL that are suitable for high-throughput screening and protein crystallization, as well as a crystallized form of monoacylglycerol lipase protein (MGLL) and descriptions of the X-ray diffraction patterns are disclosed. The engineered constructs of MGLL permit the expression and purification of protein suitable for crystallography or high-throughput screening and identification of ligands, which can function as active agents to MGLL. The X-ray diffraction patterns allow the three dimensional structure of MGLL to be determined at atomic resolution so that ligand binding sites on MGLL can be identified and the interactions of ligands with MGLL amino acid residues can be modeled. Models prepared using such maps permit the design of ligands which can function as active agents which include, but are not limited to, those that function as inhibitors of MGLL.