Association of the Inositol (1,4,5)-Trisphosphate Receptor Ligand Binding Site with Phosphatidylinositol (4,5)-Bisphosphate and Adenophostin A

2000 ◽  
Vol 3 (3) ◽  
pp. 153-158 ◽  
Author(s):  
Lyuba Glouchankova ◽  
U.Murali Krishna ◽  
Barry V.L. Potter ◽  
J.Russell Falck ◽  
Ilya Bezprozvanny
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Ligand Binding Site ◽  
Receptor Ligand ◽  
Inositol 1,4,5 Trisphosphate ◽  
Adenophostin A ◽  
Trisphosphate Receptor

scholarly journals Cooperative Formation of the Ligand-binding Site of the Inositol 1,4,5-Trisphosphate Receptor by Two Separable Domains

1999 ◽  
Vol 274 (1) ◽  
pp. 328-334 ◽  
Author(s):  
Fumio Yoshikawa ◽  
Hirohide Iwasaki ◽  
Takayuki Michikawa ◽  
Teiichi Furuichi ◽  
Katsuhiko Mikoshiba
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Ligand Binding Site ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

scholarly journals Mutational Analysis of the Ligand Binding Site of the Inositol 1,4,5-Trisphosphate Receptor

1996 ◽  
Vol 271 (30) ◽  
pp. 18277-18284 ◽  
Author(s):  
Fumio Yoshikawa ◽  
Mitsuhiro Morita ◽  
Toshiaki Monkawa ◽  
Takayuki Michikawa ◽  
Teiichi Furuichi ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Mutational Analysis ◽  
Ligand Binding Site ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

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 Ca2+ and calmodulin differentially modulate myo-inositol 1,4,5-trisphosphate (IP3)-binding to the recombinant ligand-binding domains of the various IP3 receptor isoforms

2000 ◽  
Vol 346 (2) ◽  
pp. 275-280 ◽  
Author(s):  
Sara VANLINGEN ◽  
Henk SIPMA ◽  
Patrick DE SMET ◽  
Geert CALLEWAERT ◽  
Ludwig MISSIAEN ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Recombinant Proteins ◽  
Ip3 Receptor ◽  
Binding Characteristics ◽  
Binding Domains ◽  
Receptor Isoforms ◽  
Inositol 1,4,5 Trisphosphate ◽  
Adenophostin A ◽  
Trisphosphate Receptor

We have expressed the N-terminal 581 amino acids of type 1 myo-inositol 1,4,5-trisphosphate receptor (IP3R1), IP3R2 and IP3R3 as recombinant proteins [ligand-binding site 1 (lbs-1), lbs-2, lbs-3] in the soluble fraction of Escherichia coli. These recombinant proteins contain the complete IP3-binding domain and bound IP3 and adenophostin A with high affinity. Ca2+ and calmodulin were previously found to maximally inhibit IP3 binding to lbs-1 by 42±6 and 43±6% respectively, and with an IC50 of approx. 200 nM and 3 μM respectively [Sipma, De Smet, Sienaert, Vanlingen, Missiaen, Parys and De Smedt (1999) J. Biol. Chem. 274, 12157-12562]. We now report that Ca2+ inhibited IP3 binding to lbs-3 with an IC50 of approx. 700 nM (37±4% inhibition at 5 μM Ca2+), while IP3 binding to lbs-2 was not affected by increasing [Ca2+] from 100 nM to 25 μM. Calmodulin (10 μM) inhibited IP3 binding to lbs-3 by 37±4%, while IP3 binding to lbs-2 was inhibited by only 11±2%. The inhibition of IP3 binding to lbs-3 by calmodulin was dose-dependent (IC50≈ 2 μM). We conclude that the IP3-binding domains of the various IP3R isoforms differ in binding characteristics for IP3 and adenophostin A, and are differentially modulated by Ca2+ and calmodulin, suggesting that the various IP3R isoforms can have different intracellular functions.

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

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
Sign in / Sign up

Export Citation Format

Share Document