Class-dependent sequence alignment strategy improves the structural and functional modeling of P450s

被引:33
作者
Baudry, Jerome
Rupasinghe, Sanjeewa
Schuler, Mary A.
机构
[1] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA
[2] Univ Illinois, Sch Chem Sci, Urbana, IL 61801 USA
关键词
molecular modeling; cytochrome P450 monooxygenases; P450s;
D O I
10.1093/protein/gzl012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Different procedures for obtaining homology models for P450s are investigated using various sequence alignments sharing various levels of sequence identity with available P450 crystal structures. In this analysis, we have investigated how well homology modeling can reproduce known crystal structures as well as how effectively these homology models can be used to reproduce known ligand-binding modes. Homology models obtained from sequence alignments that discriminate between Class I and Class II P450s are significantly closer to the experimental crystal structures and more closely reproduce known ligand's binding modes, than those obtained using sequence alignments that combine Class I and Class II P450s. The quality of the models is slightly improved by constructing hybrid-structure models that model three of the most variable regions of P450s independently from the rest of the protein: the B region that includes SRS1, the FG region that includes SRS2 and SRS3 and the beta 4 region that includes SRS6.
引用
收藏
页码:345 / 353
页数:9
相关论文
共 50 条
[1]   Molecular docking of substrates and inhibitors in the catalytic site of CYP6B1, an insect cytochrome P450 monooxygenase [J].
Baudry, J ;
Li, WM ;
Pan, LP ;
Berenbaum, MR ;
Schuler, MA .
PROTEIN ENGINEERING, 2003, 16 (08) :577-587
[2]   Construction and evaluation of a three-dimensional structure of cytochrome P450choP enzyme (CYP105C1) [J].
Chang, YT ;
Loew, GH .
PROTEIN ENGINEERING, 1996, 9 (09) :755-766
[3]   STRUCTURE OF CYTOCHROME P450ERYF INVOLVED IN ERYTHROMYCIN BIOSYNTHESIS [J].
CUPPVICKERY, JR ;
POULOS, TL .
NATURE STRUCTURAL BIOLOGY, 1995, 2 (02) :144-153
[4]   Cytochrome P450 in silico: An integrative modeling approach [J].
de Graaf, C ;
Vermeulen, NPE ;
Feenstra, KA .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (08) :2725-2755
[5]   Analysis of mammalian cytochrome P450 structure and function by site-directed mutagenesis [J].
Domanski, TL ;
Halpert, JR .
CURRENT DRUG METABOLISM, 2001, 2 (02) :117-137
[6]   PREDICTION OF PROTEIN 3-DIMENSIONAL STRUCTURES IN INSERTION AND DELETION REGIONS - A PROCEDURE FOR SEARCHING DATA-BASES OF REPRESENTATIVE PROTEIN-FRAGMENTS USING GEOMETRIC SCORING CRITERIA [J].
FECHTELER, T ;
DENGLER, U ;
SCHOMBURG, D .
JOURNAL OF MOLECULAR BIOLOGY, 1995, 253 (01) :114-131
[7]  
GOTOH O, 1992, J BIOL CHEM, V267, P83
[8]   How similar are P450s and what can their differences teach us? [J].
Graham, SE ;
Peterson, JA .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1999, 369 (01) :24-29
[9]   CRYSTAL-STRUCTURE AND REFINEMENT OF CYTOCHROME P450(TERP) AT 2-CENTER-DOT-3 ANGSTROM RESOLUTION [J].
HASEMANN, CA ;
RAVICHANDRAN, KG ;
PETERSON, JA ;
DEISENHOFER, J .
JOURNAL OF MOLECULAR BIOLOGY, 1994, 236 (04) :1169-1185
[10]   AMINO-ACID SUBSTITUTION MATRICES FROM PROTEIN BLOCKS [J].
HENIKOFF, S ;
HENIKOFF, JG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (22) :10915-10919