MPA3 | |
Project ID | MPA3 [Protein] |
Project Theme | Study on reactive oxygen-producing systems involved in neural cell death and structure-based discovery of their inhibitors |
Project Theme (short) | NADPH oxidase complexes |
Principal Investigator | Hideki Sumimoto |
Affiliation | Medical Institute of Bioregulation, Kyushu University |
Backgrounds | - Neurodegenerative diseases including Alzheimer's and Parkinson's occur as a result of the progressive loss of structure or function of nerve cells - Since reactive oxygen species play a variety of roles in vivo, superoxide forming NADPH oxidases (Nox) and related proteins have been implicated in neurodegenerative diseases - We will pursue structural and functional characterizations of membrane proteins Nox |
Highlights | - The structure of the NADPH interacting site of Nox2 has been determined - We could identify the essential domains of Nox2 activating proteins and started to screen compounds that inhibit the Nox2-activating proteins interactions |
Outline | Since reactive oxygen species play a variety of roles in vivo, superoxide forming NADPH oxidases (Nox) and related proteins have been implicated in neurodegenerative, cardiovascular and infectious diseases. Nox is normally latent in neutrophils and is activated to assemble in the membrane during respiratory burst. Humans have 5 types of Nox (Nox1-Nox5) and Nox1, 2 and 4 are expressed in nerve cells. We already reported our discoveries on Nox4 and proteins that activates Nox1. Nox is membrane-bound enzyme complex and generates superoxide by transferring electrons from NADPH inside the cell across the membrane and coupling the electrons to molecular oxygen to produce the superoxide. In this project, we will tackle the difficult problem of the structural determination of the membrane protein Nox to understand the electron transfer mechanism in Nox. Nox activating proteins are also our important targets. |
Review | FEBS J. |
CSML File | MPA3.csml |