College of Pharmacy - University of New Mexico

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Host:  Eric Underbakke

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"Deciphering Conformational Control of NO Synthases by an Integrated Approach"

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.