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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/28967
Title: Study of the structural pathology caused by CYP2C9 polymorphisms towards flurbiprofen metabolism using molecular dynamics simulation
Authors: Yuranat Saikatikorn
Panida Lertkiatmongkol
Anunchai Assawamakin
Marasri Ruengjitchatchawalya
Sissades Tongsima
King Mongkuts University of Technology Thonburi
Mahidol University
National Center for Genetic Engineering and Biotechnology (BIOTEC
Keywords: Computer Science
Issue Date: 6-Dec-2010
Citation: Communications in Computer and Information Science. Vol.115 CCIS, (2010), 26-35
Abstract: CYP2C9 is one of the major cytochrome P450 enzymes that play a crucial role in metabolic clearance of several drugs in the current clinical used. CYP2C9 has several allelic variant forms each of which arises from single amino acid substitution and could reduce/increase enzyme activities and affect drug metabolism. Mutant alleles may cause serious toxicity in some narrow therapeutic index drugs. CYP2C9*13, one of the CYP2C9 variant forms that is commonly found in Asian population, has a Leu90Pro amino acid substitution that leads to defective drug metabolism in individuals who carry this allele. It has been reported that metabolic activity of CYP2C9*13 was reduced towards some CYP2C9 substrates compared to wildtype. In this study, X-ray crystal structure of human cytochrome P450 2C9 complexed with flurbiprofen (PDB code: 1R9O) was represented to wildtype and the structure of CYP2C9*13 was constructed based on the X-ray crystal structure of CYP2C9-flurbiprofen complex. Herein, molecular docking of CYP2C9*1 and CYP2C9*13 with flurbiprofen was performed in search for flurbiprofen orientation that corresponds to its binding state before undergoing monooxygenation. Subsequently, molecular dynamics simulation was operated to compare binding of flurbiprofen in catalytic cavity of these 2 variants. Substrate access channel of CYP2C9*13 has a dramatic effect on an interaction between the drug and the enzyme. Consequently, this study can lead to an understanding of structural pathology caused by single amino acid change in CYP2C9*13 variant. © 2010 Springer-Verlag Berlin Heidelberg.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=78649573472&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/28967
ISSN: 18650929
Appears in Collections:Scopus 2006-2010

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