This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The respiratory chains of mitochondria and bacteria convert electrochemical redox energy from the oxidation of substrates into an electrochemical gradient of the hydrogen ion, which can be utilized for energy-requiring processes such as ATP generation and active transport. The energy coupling between electron transfer reactions and proton translocation is carried out by multi-subunit membrane protein complexes. In addition to their biological importance, these are good membrane proteins to get started with because of their high abundance in the cell which obviates the need for overexpression. A mature project is the cytochrome bc1 complex (Complex III), which we have crystallized from a number of organism. Now we are studying binding mode of inhibitors and substrates, looking at conformational changes, and pushing the resolution (2.0 ? so far) by optimizing dehydration and freezing conditions. For Complex II we have crystallized the avian enzyme and phased the crystals, now we are working on improving resolution and solving the structure. With Complex I we are still screening crystallization conditions.
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