Structural investigation of ATP-utilizing enzymes: Structures involved in hydrogen homeostasis and the proliferation of hormone-dependent cancers
ATP is a multifunctional nucleotide considered to be the “molecular unit of currency” of intracellular energy transfer. ATP is utilized ubiquitously for the transport of chemical energy within the cell in addition to acting as a substrate in the regulation of many metabolic and signaling transduction pathways such as kinase-mediated signaling cascades. Interestingly, the functional mechanisms of many enzymes require the binding of ATP to trigger key structural and conformational changes that ultimately result in enzyme-directed catalysis. Two of the most omnipresent ATPases within the cell include the V-ATPase rotary proton pump and the Hsp90 protein-folding chaperone. Structural and biochemical investigations of these enzymes reveal interesting details and novel binding interactions that further illustrate the role ATP hydrolysis plays in both the translocation of protons across membranes and hormone receptor activation, respectively. The 14Å cryo-EM reconstruction of the hydrophilic V1-ATPase provides insight into the architecture of the peripheral stator stalks as well as revealing a unique inhibitory interaction between the DF central rotor and the A3B3 catalytic complex. Additionally, the formation of the Hsp90-FKBP52-p23-HOP complex highlights the simultaneous binding of two TPR domain-containing proteins to the Hsp90 chaperone. These particular interactions support the existence of a novel sub-assembly potentially involved in the regulation of steroid hormone receptor-mediated transcriptional activity. Collectively the two investigations described below illustrate the omnipotent role ATP plays in the context of cellular physiology.
Hildenbrand, Zacariah Louis, "Structural investigation of ATP-utilizing enzymes: Structures involved in hydrogen homeostasis and the proliferation of hormone-dependent cancers" (2010). ETD Collection for University of Texas, El Paso. AAI3433482.