Molecular localization and characterization of multiple binding sites of organic anion transporting polypeptide 2B1 (OATP2B1) as the mechanism for substrate and modulator dependent drug–drug interaction

MedChemComm ◽  
2016 ◽  
Vol 7 (9) ◽  
pp. 1775-1782 ◽  
Author(s):  
Yusuke Hoshino ◽  
Daichi Fujita ◽  
Takeo Nakanishi ◽  
Ikumi Tamai
Keyword(s):  
Drug Interaction ◽  
Binding Sites ◽  
Organic Anion ◽  
Schematic Model ◽  
Organic Anion Transporting Polypeptide ◽  
Multiple Binding Sites ◽  
Multiple Binding ◽  
Drug Drug Interaction ◽  
The Relationship

Schematic model of the relationship and locations of putative binding sites of substrates and modulators in OATP2B1. Drug–drug interaction and drug–food interaction on OATP2B1 can be predicted by clarification of multiple binding sites.

Functional Pleiotropy of Organic Anion Transporting Polypeptide OATP2B1 Due to Multiple Binding Sites

2012 ◽  
Vol 27 (3) ◽  
pp. 360-364 ◽  
Author(s):  
Yoshiyuki Shirasaka ◽  
Takanori Mori ◽  
Megumi Shichiri ◽  
Takeo Nakanishi ◽  
Ikumi Tamai
Keyword(s):  
Binding Sites ◽  
Organic Anion ◽  
Organic Anion Transporting Polypeptide ◽  
Multiple Binding Sites ◽  
Multiple Binding

The characterization of ATPases from the gill of the osteoglossid Osteoglossum bicirrhosum (aruaná)

1978 ◽  
Vol 56 (4) ◽  
pp. 795-800 ◽  
Author(s):  
Thomas W. Moon
Keyword(s):  
Ion Transport ◽  
Divalent Cation ◽  
Binding Sites ◽  
Microsomal Fraction ◽  
Specific Interaction ◽  
Cation Activation ◽  
Multiple Binding Sites ◽  
Monovalent Ions ◽  
Multiple Binding

Gill ATPases of the osteoglossid Osteoglossum bicirrhosum (aruaná) were isolated from the microsomal fraction (Nal pellet) and assayed in the presence of various cations and anions. The presence of Ca2+, Mg2+ (Mn2+), Na+ + K+ (with Mg2+) activated ATP hydrolyses; activation by Ca2+ and Mg2+ was similar and both were inhibited by thiocyanate, but the monovalent ions showed much lower activities. Activities in the presence of these ions were in the range reported for temperate teleosts such as the eel, goldfish, or trout. No HCO3− or NH4+ activation was detected. Apparent Km values for divalent cation activation were well above their respective environmental concentrations, but within the range reported for analogous enzymes of temperate teleosts. There is a specific interaction between Ca2+ and Mg2+ binding to the enzyme, but the results cannot distinguish between the existence of one enzyme with multiple binding sites, or a numberof ion-specific ATPases. These results suggest that the enzyme s assayed in this investigation are only indirectly, if at all, associated with gill ion transport in aruaná.

NMDAR PAMs: Multiple Chemotypes for Multiple Binding Sites

2019 ◽  
Vol 19 (24) ◽  
pp. 2239-2253 ◽  
Author(s):  
Paul J. Goldsmith
Keyword(s):  
Binding Sites ◽  
Receptor Activation ◽  
Research Area ◽  
Allosteric Modulators ◽  
Nonselective Cation Channels ◽  
Multiple Binding Sites ◽  
Multiple Binding ◽  
Excitatory Neurotransmission ◽  
Psychiatric Conditions ◽  
High Level

The N-methyl-D-aspartate receptor (NMDAR) is a member of the ionotropic glutamate receptor (iGluR) family that plays a crucial role in brain signalling and development. NMDARs are nonselective cation channels that are involved with the propagation of excitatory neurotransmission signals with important effects on synaptic plasticity. NMDARs are functionally and structurally complex receptors, they exist as a family of subtypes each with its own unique pharmacological properties. Their implication in a variety of neurological and psychiatric conditions means they have been a focus of research for many decades. Disruption of NMDAR-related signalling is known to adversely affect higherorder cognitive functions (e.g. learning and memory) and the search for molecules that can recover (or even enhance) receptor output is a current strategy for CNS drug discovery. A number of positive allosteric modulators (PAMs) that specifically attempt to overcome NMDAR hypofunction have been discovered. They include various chemotypes that have been found to bind to several different binding sites within the receptor. The heterogeneity of chemotype, binding site and NMDAR subtype provide a broad landscape of ongoing opportunities to uncover new features of NMDAR pharmacology. Research on NMDARs continues to provide novel mechanistic insights into receptor activation and this review will provide a high-level overview of the research area and discuss the various chemical classes of PAMs discovered so far.

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