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Molecular dynamics study on the ligand recognition by tandem SH3 domains of p47phox, regulating NADPH oxidase activity

Paper ID Volume ID Publish Year Pages File Format Full-Text
15567 1430 2006 10 PDF Available
Title
Molecular dynamics study on the ligand recognition by tandem SH3 domains of p47phox, regulating NADPH oxidase activity
Abstract

The phagocyte NADPH oxidase complex plays a crucial role in host defense against microbial infection through the production of superoxides. Chronic granulomatous disease (CGD) is an inherited immune deficiency caused by the absence of certain components of the NADPH oxidase. Key to the activation of the NADPH oxidase is the cytoplasmic subunit p47phox, which includes the tandem SH3 domains (N-SH3 and C-SH3). In active phagocytes, p47phox forms a stable complex with the cytoplasmic region of membrane subunit p22phox that forms a left-handed polyproline type-II (PPII) helix conformation. In this report, we have analyzed the conformational changes of p47phox–p22phox complexes of wild-type and three mutants, which have been detected in CGD patients, using molecular dynamics simulations. We have found that in the wild-type, two basal planes of PPII prism in cytoplasmic region of p22phox interacted with N-SH3 and C-SH3. In contrast, in the modeled mutants, the residue at the ape of PPII helix, which interacts simultaneously with both of the tandem SH3 domains in the wild-type, moved toward C-SH3. Furthermore, interaction energies of the cytoplasmic region of p22phox with C-SH3 tend to decrease in these mutants. All these findings led us to conclude that interactions between N-SH3 of p47phox and PPII helix, which is formed by cytoplasmic region of p22phox, may play a significant role in the activation of the NADPH oxidase.

Keywords
Molecular dynamics; NADPH oxidase; SH3 domain; PPII helix; Ligand recognition
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Molecular dynamics study on the ligand recognition by tandem SH3 domains of p47phox, regulating NADPH oxidase activity
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 30, Issue 4, August 2006, Pages 303–312
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us