scholarly journals Invariant Aspartic Acid in Muscle Nicotinic Receptor Contributes Selectively to the Kinetics of Agonist Binding

2004 ◽  
Vol 124 (5) ◽  
pp. 555-567 ◽  
Author(s):  
Won Yong Lee ◽  
Steven M. Sine
Keyword(s):  
Hydrogen Bond ◽  
Ligand Binding ◽  
Binding Site ◽  
Nicotinic Receptor ◽  
Negative Charge ◽  
Homology Model ◽  
Ligand Binding Site ◽  
Receptor Ligand ◽  
Kinetics Of ◽  
Hydrogen Bond Donors

We examined functional contributions of interdomain contacts within the nicotinic receptor ligand binding site using single channel kinetic analyses, site-directed mutagenesis, and a homology model of the major extracellular region. At the principal face of the binding site, the invariant αD89 forms a highly conserved interdomain contact near αT148, αW149, and αT150. Patch-clamp recordings show that the mutation αD89N markedly slows acetylcholine (ACh) binding to receptors in the resting closed state, but does not affect rates of channel opening and closing. Neither αT148L, αT150A, nor mutations at both positions substantially affects the kinetics of receptor activation, showing that hydroxyl side chains at these positions are not hydrogen bond donors for the strong acceptor αD89. However substituting a negative charge at αT148, but not at αT150, counteracts the effect of αD89N, demonstrating that a negative charge in the region of interdomain contact confers rapid association of ACh. Interpreted within the structural framework of ACh binding protein and a homology model of the receptor ligand binding site, these results implicate main chain amide groups in the domain harboring αW149 as principal hydrogen bond donors for αD89. The specific effect of αD89N on ACh association suggests that interdomain hydrogen bonding positions αW149 for optimal interaction with ACh.

scholarly journals Alanine Scanning Mutagenesis of a Type 1 Insulin-like Growth Factor Receptor Ligand Binding Site

2001 ◽  
Vol 276 (47) ◽  
pp. 43980-43986 ◽  
Author(s):  
Jonathan Whittaker ◽  
Andreas V. Groth ◽  
Dennis C. Mynarcik ◽  
Lene Pluzek ◽  
Vibeke L. Gadsbøll ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ligand Binding ◽  
Binding Site ◽  
Growth Factor Receptor ◽  
Insulin Like Growth Factor ◽  
Ligand Binding Site ◽  
Alanine Scanning Mutagenesis ◽  
Receptor Ligand ◽  
Alanine Scanning

74Probing the structure of the ligand binding site on the muscle nicotinic receptor with Waglerin peptides

1998 ◽  
Vol 92 (5-6) ◽  
pp. 470-471 ◽  
Author(s):  
B.E. Molles ◽  
E.F. Kline ◽  
S.M. Sine ◽  
J.J. McArdle ◽  
P. Taylor
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Nicotinic Receptor ◽  
Ligand Binding Site

scholarly journals Identification of a ligand-binding site in an immunoglobulin fold domain of the Saccharomyces cerevisiae adhesion protein alpha-agglutinin.

1996 ◽  
Vol 7 (1) ◽  
pp. 143-153 ◽  
Author(s):  
H de Nobel ◽  
P N Lipke ◽  
J Kurjan
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ligand Binding ◽  
Binding Site ◽  
Mutational Analysis ◽  
Homology Model ◽  
Ligand Binding Site ◽  
Adhesion Protein ◽  
Interaction Sites ◽  
Critical Residue ◽  
Immunoglobulin Fold

The Saccharomyces cerevisiae adhesion protein alpha-agglutinin (Ag alpha 1p) is expressed by alpha cells and binds to the complementary a-agglutinin expressed by a cells. The N-terminal half of alpha-agglutinin is sufficient for ligand binding and has been proposed to contain an immunoglobulin (Ig) fold domain. Based on a structural homology model for this domain and a previously identified critical residue (His292), we made Ag alpha 1p mutations in three discontinuous patches of the domain that are predicted to be in close proximity to His292 in the model. Residues in each of the three patches were identified that are important for activity and therefore define a putative ligand binding site, whereas mutations in distant loops had no effect on activity. This putative binding site is on a different surface of the Ig fold than the defined binding sites of immunoglobulins and other members of the Ig superfamily. Comparison of protein interaction sites by structural and mutational analysis has indicated that the area of surface contact is larger than the functional binding site identified by mutagenesis. The putative alpha-agglutinin binding site is therefore likely to identify residues that contribute to the functional binding site within a larger area that contacts a-agglutinin.

scholarly journals Simulations of a G protein-coupled receptor homology model predict dynamic features and a ligand binding site

FEBS Letters ◽  
2008 ◽  
Vol 582 (23-24) ◽  
pp. 3335-3342 ◽  
Author(s):  
Steffen Wolf ◽  
Marcus Böckmann ◽  
Udo Höweler ◽  
Jürgen Schlitter ◽  
Klaus Gerwert
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
G Protein ◽  
Homology Model ◽  
Ligand Binding Site ◽  
Dynamic Features ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Varenicline Interactions at the 5-HT3 Receptor Ligand Binding Site are Revealed by 5-HTBP

2015 ◽  
Vol 6 (7) ◽  
pp. 1151-1157 ◽  
Author(s):  
Kerry L. Price ◽  
Reidun K. Lillestol ◽  
Chris Ulens ◽  
Sarah C.R. Lummis
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Ligand Binding Site ◽  
Receptor Ligand

Characterization of the human oxytocin receptor ligand binding site

1997 ◽  
Vol 25 (3) ◽  
pp. 436S-436S ◽  
Author(s):  
NICOLA. J. YARWOOD ◽  
JOHN HOWL ◽  
MARK WHEATLEY
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Oxytocin Receptor ◽  
Ligand Binding Site ◽  
Receptor Ligand

scholarly journals Molecular Modeling of Quercetin Binding to the Peroxisome Proliferator-Activated Receptor-Gamma

2011 ◽  
Vol 68 (2) ◽  
Author(s):  
Cristina COMAN (ISVORANU) ◽  
Carmen SOCACIU
Keyword(s):  
Hydrogen Bond ◽  
Molecular Modeling ◽  
Ligand Binding ◽  
Binding Site ◽  
Binding Mode ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Peroxisome Proliferator ◽  
Receptor Ligand ◽  
Peroxisome Proliferator Activated Receptor

The interaction between the quercetin (a generic flavonoid molecule) and the ligand binding domain of the peroxisome proliferator–activated receptor-gamma was investigated using the AutoDock software, which allows docking of molecular ligands to receptor macromolecules. AutoDock is able to find the most favourable binding site for quercetin on the receptor ligand binding domain and to predict the binding mode. The results show that the bonding is mainly driven through hydrogen bond type interactions and suggest the existence of two favourable quercetin conformations which coexist.

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