Muscarinic receptors: A comparative analysis of structural features and binding modes through homology modelling and molecular docking.
Three-dimensional models of the five human muscarinic receptors were obtained from their known sequences. Homology modelling based on the crystallographic structure of bovine rhodopsin yielded models compatible with known results from site-directed mutagenesis studies. The only exceptions were the cytoplasmic loop 3 (CL3) in the five receptors, and the large C-terminal domain in M(1). Here, homology modelling with other closely related proteins allowed to solve these gaps. A detailed comparative discussion of the five models is given. The second part of the work involved docking experiments with the physiological ligand acetylcholine, again yielding results entirely compatible with results from mutagenesis experiments. The study revealed analogies and differences between the five receptors in the residues, and interactions leading to the recognition and binding of acetylcholine.
Pedretti
Alessandro
A
Istituto di Chimica Farmaceutica, Facoltà di Farmacia, Università di Milano, Viale Abruzzi 42, I-20131 Milano, Italy.
Vistoli
Giulio
G
Marconi
Cristina
C
Testa
Bernard
B
D000109:Acetylcholine / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010802:Phylogeny; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011976:Receptors, Muscarinic / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D040681:Structural Homology, Protein
D011976:Receptors, Muscarinic; D000109:Acetylcholine