Identification of the Critical Residues of Bradykinin Receptor B1 for Interaction with the Kinins Guided by Site-Directed Mutagenesis and Molecular Modeling
| Autor: | J. Fred Hess, Kathryn L. Murphy, Mark G. Bock, Rick W. Ransom, Dai-Shi Su, Douglas J. Pettibone, Tsing-Bau Chen, R. S. L. Chang, Sookhee Ha, Pat J. Hey |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Molecular Sequence Data Bradykinin Peptide Kinins Receptor Bradykinin B1 Biochemistry Protein Structure Secondary chemistry.chemical_compound Animals Humans Amino Acid Sequence Homology modeling Bradykinin receptor Protein Structure Quaternary Site-directed mutagenesis Receptor Bradykinin receptor B1 Conserved Sequence chemistry.chemical_classification Binding Sites Cell Membrane Ligand (biochemistry) chemistry Mutation Mutagenesis Site-Directed Sequence Alignment Protein Binding |
| Zdroj: | Biochemistry. 45:14355-14361 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi060673f |
| Popis: | We report the critical residues for the interaction of the kinins with human bradykinin receptor 1 (B1) using site-directed mutagenesis in conjunction with molecular modeling of the binding modes of the kinins in the homology model of the B1 receptor. Mutation of Lys118 in transmembrane (TM) helix 3, Ala270 in TM6, and Leu294 in TM7 causes a significant decrease in the affinity for the peptide agonists des-Arg10kallidin (KD) and des-Arg9BK but not the peptide antagonist des-Arg10Leu9KD. In contrast, mutations in TM2, TM3, TM6, and TM7 cause a significant decrease in the affinity for both the peptide agonists and the antagonist. These data indicate that the B1 bradykinin binding pocket for agonists and antagonists is similar, but the manners in which they interact with the receptor do not completely overlap. Therefore, there is a potential to influence the receptor's ligand selectivity. |
| Databáze: | OpenAIRE |
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