Department of Chemistry and Chemical Biology - University of New Mexico
Host: Eric Underbakke
"Dissecting Regulation Mechanism of Nitric Oxide Synthase by Conformational Dynamics"
Electron transfer is a fundamental process in life that is very often coupled to catalysis within redox enzymes through a stringent control of protein conformational movements. Mammalian NOS proteins are redox flavo-hemoproteins consisting of multiple modular domains. The NOS enzyme is exquisitely regulated in vivo by its partner, the Ca2+ sensing protein calmodulin (CaM), to control production of NO. The importance of functional domain motion in NOS regulation has been increasingly recognized.
Despite recent progress in revealing the architecture of full-length NOS proteins, the details of how CaM and the control elements function at the molecular level to regulate the NOS domain dynamics and control the obligatory electron transfer steps remain unclear. The large size and dynamic nature of NOS proteins necessitate an implementation of a synergistic approach combining the pulsed EPR spectroscopy with functional and kinetics studies to achieve a molecular-level understanding of NOS regulation.