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Computer molecular modelling of the p22phox protein structural changes linked to C242T polymorphism

Howlin, BJ, Meijles, DN and Li, JM (2011) Computer molecular modelling of the p22phox protein structural changes linked to C242T polymorphism In: PROCEEDINGS OF THE BPS Clinical Pharmaclgy Section, 2010-12-14 - 2010-12-16, QUEEN ELIZABETH II CONFERENCE CENTRE, LONDON.

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Abstract

The p22phox is a key component of the cytochrome b558 of the NADPH oxidase (Nox), which by generating reactive oxygen species (ROS) is involved in the pathogenesis of cardiovascular disease. A p22phox polymorphism (C242T) has been found to reduce oxidative stress in the cardiovascular system and is negatively associated with the incidence of coronary heart disease (CHD). However, the mechanism involved remains unknown. In this study we used computer molecular modelling and bioinformatics to investigate the potential effect of C242T polymorphism on the 3-D protein structure of the p22phox. Based on the published sequence data of p22phox and the principle of regulated prediction algorithms, we found that p22phox consists of two domains: an N-terminal transmembrane domain (124 a.a.) and a C-terminal cytoplasmic domain (71 a.a.). In its most stable form, it has three transmembrane helices leading to an extracellular N-terminus and an extracellular loop between helices two and three. The C242T polymorphism causes a change of His72 to Tyr72. This change results in signifi cant morphological changes of the extracellular loop of the p22phox which is in the putative interactive region of the p22phox with the catalytic subunit (Nox2). This may interfere with their association, and subsequently result in a reduced cytochrome b function and a reduced ROS production by NADPH oxidase. These results give us insight into the molecular mechanism of this polymorphism in reducing vascular oxidative stress and may explain how this polymorphism is linked with reduced incidence of CHD.

Item Type: Conference or Workshop Item (UNSPECIFIED)
Authors :
NameEmailORCID
Howlin, BJb.howlin@surrey.ac.ukUNSPECIFIED
Meijles, DNUNSPECIFIEDUNSPECIFIED
Li, JMUNSPECIFIEDUNSPECIFIED
Date : 1 June 2011
Identification Number : 10.1111/j.1365-2125.2011.03930.x
Uncontrolled Keywords : cARDIOVASCULAR, mOLECULAR MODELLING
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 12:21
Last Modified : 17 May 2017 15:03
URI: http://epubs.surrey.ac.uk/id/eprint/835010

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