Dr. Kaplan's research interest is the structure, function, and regulation of mitochondrial anion transport proteins at the molecular and atomic levels. A major focus of this laboratory concerns the mitochondrial citrate transport protein (i.e., CTP) since this carrier occupies a fundamentally important position within hepatic intermediary metabolism. Using an array of biochemical and biophysical we are attempting to:
- Identify those amino acid residues which comprise the substrate binding site(s) and translocation pathway through the CTP;
- Identify residues that form the interf
- Develop conditions permitting the growth of X-ray quality crystals of the CTP, thereby setting the stage for a high resolution 3-dimensional structure of this metabolically important carrier.
|Depiction of elements of the substrate translocation pathway within the homology-modeled structure of the mitochondrial citrate transport protein. This panel depicts a view into the transport pathway from the cytosolic face of the lipid bilayer. Residues within transmembrane domain III that are protected by substrate and thus likely line the pathway are depicted in red, while those that are not protected and face away from the pathway are depicted in blue. Q182 (orange) may sterically block L120 (blue) even though L120 faces the pathway.
||Two citrate binding sites within the CTP transport pathway viewed in the plane of the membrane bilayer. Two citrate binding sites, viewed in the plane of the membrane bilayer (i.e., a side view) are presented. The backbone of the CTP is represented as a green ribbon. Important side chains are shown as stick structures, and citrate molecules are shown as spacefilling structures. Citrate oxygens are red. In site one, the citrate carbons and the directly interacting side chains are magenta; in site two, the citrate carbons and the directly interacting side chains are cyan. The distance between the two sites (measuring at the central carbon atoms of the two citrates) is 9.2 Å. Portions of TMDs I, II, and VI have been cut away for clarity. Black horizontal lines at right indicate the approximate boundaries of the bilayer and the atomic ruler at the left indicates approximate dimensions.