Abstract
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 β4 region that includes SRS6.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 345-353 |
| Number of pages | 9 |
| Journal | Protein Engineering, Design and Selection |
| Volume | 19 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2006 |
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Keywords
- Cytochrome P450 monooxygenases
- Molecular modeling
- P450s
ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Biochemistry
- Molecular Biology
Cite this
Class-dependent sequence alignment strategy improves the structural and functional modeling of P450s. / Baudry, Jerome; Rupasinghe, Sanjeewa; Schuler, Mary A.
In: Protein Engineering, Design and Selection, Vol. 19, No. 8, 01.08.2006, p. 345-353.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Class-dependent sequence alignment strategy improves the structural and functional modeling of P450s
AU - Baudry, Jerome
AU - Rupasinghe, Sanjeewa
AU - Schuler, Mary A.
PY - 2006/8/1
Y1 - 2006/8/1
N2 - 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 β4 region that includes SRS6.
AB - 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 β4 region that includes SRS6.
KW - Cytochrome P450 monooxygenases
KW - Molecular modeling
KW - P450s
UR - http://www.scopus.com/inward/record.url?scp=33745911122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745911122&partnerID=8YFLogxK
U2 - 10.1093/protein/gzl012
DO - 10.1093/protein/gzl012
M3 - Article
C2 - 16777908
AN - SCOPUS:33745911122
VL - 19
SP - 345
EP - 353
JO - Protein Engineering, Design and Selection
JF - Protein Engineering, Design and Selection
SN - 1741-0126
IS - 8
ER -