The main focus of my laboratory is the structure-function investigation of membrane-associated proteins.  To date the atomic structures of only a handful of membrane proteins are known.  Recently, we solved the atomic resolution structure of bacteriorhodopsin (BR), a light-driven proton pump.  We are also studying annexins, a family of proteins which interact with phospholipid bilayers in a Ca²⁺-dependent manner.  Annexins have been reported to mediate membrane aggregation and fusion, as well as ion channel formation.  Detailed structural studies of annexins are essential for understanding their fusogenic and ion channel forming properties at the atomic level.  The lab is also working on the structure of other integral membrane proteins such as a water channel (MIP), and a voltage-gated potassium ion channel (Kv1.3).

A second area of interest is rational drug design based on crystal structures.  We have recently solved the structure of a key enzyme in purine metabolism, inosine-5'-monophosphate dehydrogenase (IMPDH).  IMPDH catalyzes the NAD-dependent conversion of IMP to XMP which in turn is converted to GMP, an essential building block of DNA.  The IMPDH-reaction is the rate-limiting step in GMP synthesis and is thus a promising target for anti-parasitic and anti-bacterial drugs.  We are currently focusing on IMPDH from P. falciparum, M. tuberculosis. and T. foetus.

Another interest of my group are very high resolution (1.0 Å or better) structures of phosphate binding protein.  These studies require synchrotron-generated X-rays of very high brilliance.  Atomic structures at this resolution are able to reveal details of hydrogen bonding that cannot be obtained by other methods.

• X-ray crystallography
• 2D electron diffraction
• Freeze-fracture electron microscopy
• Small angle x-ray and dynamic light scattering
• Molecular modeling & docking

• High specificity of a phosphate transport protein determined by hydrogen bonds.  H Luecke & FA Quiocho  (1990) Nature 347, 402-406.
• Dipoles localized at helix termini of proteins stabilize charges.  J Aquist, H Luecke, FA Quiocho & A Warshel  (1991) Proc. Natl. Acad. Sci. USA 88, 2026-2030.
• Crystal structure of the annexin XII hexamer and implications for bilayer insertion.  H Luecke, BT Chang, WS Mailliard, DD Schlaepfer & HT Haigler  (1995) Nature 378, 512-515.
• A low energy short hydrogen bond in very high resolution structures of protein receptor-phosphate complexes.  Z Wang, H Luecke, N Yoa & FA Quiocho  (1997) Nature Structural Biology, 4, 519-522.
• Tritrichomonas foetus: a strategy for structure-based inhibitor design of a protozoan inosine-5'-monophosphate dehydrogenase.  H Luecke, GL Prosise & FG Whitby  (1997) Exp. Parasitol. 87, 203-211.
• Proton Transfer Pathways in Bacteriorhodopsin at 2.3 Angstrom Resolution.  H Luecke, H-T Richter & JK Lanyi  (1998) Science 280, 1934-1937.

• The Hudel Lab.
• The Structural Biology Program (Protein Crystallography) at UC Irvine.
• Structural biology graduate studies at UC Irvine.
• A brief outdated DENZO tutorial.
• Lecture notes for my section of BioSci 99A (Spring 1998)

To update this Web page, please contact Einstein@uci.edu