Charge density studies as a tool in drug design
David E. Hibbs, Trevor W. Hambley, Graham A.R. Johnston, Jane R. Hanrahan · Acta Crystallographica Section A Foundations of Crystallography · 2002
Cytochrome c oxidase, a terminal respiratory enzyme complex, accepts electrons from cytochrome c and reduces dioxygens to waters coupling with pumping protons across the membrane.X-ray structures of bovine heart enzyme at the fully oxidized, reduced and several ligand-binding states at 280 K have been determined (1-4).The enzyme consists of two copies of 13 different subunits.The transmembrane part of each monomer consists of 28 αhelices, including metal centers of hemes a and a3 and CuB at the same level in the membrane.Another metal center, CuA, is located in the intermembrane part.Possible electron and chemical proton transfer pathways, as well as a proton pumping mechanism, have been proposed (3).The crystals diffracting X-rays up to 1.65 Å were recently obtained by using ethyleneglycole as a cryoprotectant.X-ray diffraction data were collected on the image plate of DIP2040 (MAC SCIENCE) at BL44XU of the SPring-8.Structures were determined by the molecular replacement method.Now, we have 1.8 Å oxidized and 1.9 Å reduced structures at 100 K, as well as 2.3 Å oxidized and 2.35 Å reduced enzyme structures at 280 K. Several novel water arrangements functioning in proton translocation were detected by inspecting these structures at both 100 K and 280 K References (1) Tsukihara et al. (1995)