Cytochromes P450 (CYPs) play an important role in the oxidative metabolism of xenobiotics. Three-dimensional structures of CYPs are needed to study structure-function relationships in their molecules and interaction with partner proteins. Experimental determination of eucaryotic CYPs 3D structures is difficult because of hydrophobic membrane anchors and surface hydrophobic regions that prevent their crystallization. Replacement of surface hydrophobic amino acids by hydrophilic residues without any changes in protein structure and function can help to solve this problem. Such modification can be proposed using the analysis of 3D model of protein. In this work computer aided 3D structure of microsomal P450 2B4 (CYP2B4) was modelled for the further prediction of surface mutations for hydrophilization of the protein surface. The model of 3D structure of CYP2B4 was constructed by homology with CYP2C5. Model optimization was made by energy minimization and molecular dynamics simulation of protein molecule in water environment. The model was verified by using special statistic software and by comparison with the experimental data on the substrate recognition site, redox-partner binding sites and chemical modification of the protein surface
Download PDF:
Citation:
Sechenykh A.A., Dubanov A.V., Skvortsov V.S., Ivanov A.S., Archakov A.I., Williams P., Cosme J., Johnson E.F., McRee D.E. (2002) Computer model of 3D structure of cytochrome P450 2B4. Voprosy Meditsinskoi Khimii, 48(5), 526-538.
Sechenykh A.A. et al. Computer model of 3D structure of cytochrome P450 2B4 // Voprosy Meditsinskoi Khimii. - 2002. - V. 48. -N 5. - P. 526-538.
Sechenykh A.A. et al., "Computer model of 3D structure of cytochrome P450 2B4." Voprosy Meditsinskoi Khimii 48.5 (2002): 526-538.
Sechenykh, A. A., Dubanov, A. V., Skvortsov, V. S., Ivanov, A. S., Archakov, A. I., Williams, P., Cosme, J., Johnson, E. F., McRee, D. E. (2002). Computer model of 3D structure of cytochrome P450 2B4. Voprosy Meditsinskoi Khimii, 48(5), 526-538.
References
Shimoji M., Yin H., Higgins L., Jones J.P. (1998) Biochemistry. 37, 8848- 8852. Scholar google search
Hasemann C.A., Ravichandran K.G., Peterson J.A., Deisenhofer J. (1994) J. Mol. Biol. 236, 1169- 1185. Scholar google search
Ivanov A.S., Skvortsov V.S., Archakov A.I. (1996) XI International Symposium on Microsomes and Drug Oxidation, Los Angeles, USA, 1996, July 21- 24, P133. Scholar google search
Ivanov A.S., Skvortsov V.S., Dubanov A.V., Archakov A.I. The First Electronic Molecular Graphics and Modelling Society Conference (MGMS EC- 1) on the Internet and World Wide Web, 1996, Oct 7- 18, http:/bellatrix.pcl.ox.ac.uk/mgms/cornf/sect_area/pstruct/papers/ivanov2/index.html. Scholar google search
Chang Y.T., Stiffelman O.В., Vakser I.A. , Loew G.H., Bridges A., Waskell L. (1997) Protein. Eng. 10, 2, 119- 129. Scholar google search
Ivanov A.S., Dubanov A.V., Sechenykh A.A., Skvortsov V.S., Archakov A.I. International Workshop "From Sequence to Function: Experimental and Bioinformatic Studies of Cytochrome P450 Superfamily" Moscow, 2000, 3. Scholar google search
Sybyl 6.7, Tripos Inc., 1699 South Hanley Road, St Louis, Missouri, 63144, USA. Scholar google search
