Journal
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
Volume 1794, Issue 7, Pages 1066-1072Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbapap.2009.03.021
Keywords
Cytochrome P450; CYP2C38; CYP2C39; Homology modeling; Molecular dynamics; Molecular docking
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Funding
- Natural Science Foundation of China [20573042]
- Key Projects in the National Science and Technology Pillar Program [2006BAE03B01]
- Specialized Research Fund for the Doctoral Program of Higher Education [20070183046]
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Mouse CYP2C38 and CYP2C39 are two closely related enzymes with 91.8% sequence identity. But they exhibit different substrate binding features. In this study. three-dimensional models of CYP2C38 and CYP2C39 were constructed using X-ray crystal structure of human CYP2C8 as the template based on homology modeling methods and molecular dynamics simulations. Tolbutamide as the common substrate of CYP2C38 and CYP2C39 was docked into them and positioned in their active sites with different orientation. All-trans retinoic acid (atRA) is a specific substrate for CYP2C39 and not catalyzed by CYP2C38. By comparison of active site architectures between CYP2C38 and CYP2C39, the possible reasons affecting their substrate binding were proposed. In addition, Arg241, Glu300, Leu366 and Leu476 are identified as critical residue for substrates binding. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.
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