Antiulcer agents. 5. Inhibition of gastric H+/K+-ATPase by substituted imidazo[1,2-a]pyridines and related analogs and its implication in modeling the high affinity potassium ion binding site of the gastric proton pump enzyme

1991 ◽  
Vol 34 (2) ◽  
pp. 533-541 ◽  
Author(s):  
James J. Kaminski ◽  
Bjorn Wallmark ◽  
Carin Briving ◽  
Britt Marie Andersson
Keyword(s):  
Binding Site ◽  
Proton Pump ◽  
Potassium Ion ◽  
Ion Binding ◽  
High Affinity ◽  
Antiulcer Agents ◽  
Gastric Proton Pump

scholarly journals Functional characterization of the dimerization domain of the ferric uptake regulator (Fur) of Pseudomonas aeruginosa

2006 ◽  
Vol 400 (3) ◽  
pp. 385-392 ◽  
Author(s):  
Erdeni Bai ◽  
Federico I. Rosell ◽  
Bao Lige ◽  
Marcia R. Mauk ◽  
Barbara Lelj-Garolla ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Metal Ions ◽  
Binding Site ◽  
Metal Ion ◽  
Association Constants ◽  
Ion Binding ◽  
Ferric Uptake Regulator ◽  
Metal Ion Binding ◽  
Dimerization Domain ◽  
High Affinity

The functional properties of the recombinant C-terminal dimerization domain of the Pseudomonas aeruginosa Fur (ferric uptake regulator) protein expressed in and purified from Escherichia coli have been evaluated. Sedimentation velocity measurements demonstrate that this domain is dimeric, and the UV CD spectrum is consistent with a secondary structure similar to that observed for the corresponding region of the crystallographically characterized wild-type protein. The thermal stability of the domain as determined by CD spectroscopy decreases significantly as pH is increased and increases significantly as metal ions are added. Potentiometric titrations (pH 6.5) establish that the domain possesses a high-affinity and a low-affinity binding site for metal ions. The high-affinity (sensory) binding site demonstrates association constants (KA) of 10(±7)×106, 5.7(±3)×106, 2.0(±2)×106 and 2.0(±3)×104 M−1 for Ni2+, Zn2+, Co2+ and Mn2+ respectively, while the low-affinity (structural) site exhibits association constants of 1.3(±2)×106, 3.2(±2)×104, 1.76(±1)×105 and 1.5(±2)×103 M−1 respectively for the same metal ions (pH 6.5, 300 mM NaCl, 25 °C). The stability of metal ion binding to the sensory site follows the Irving–Williams order, while metal ion binding to the partial sensory site present in the domain does not. Fluorescence experiments indicate that the quenching resulting from binding of Co2+ is reversed by subsequent titration with Zn2+. We conclude that the domain is a reasonable model for many properties of the full-length protein and is amenable to some analyses that the limited solubility of the full-length protein prevents.

scholarly journals A single K+-binding site in the crystal structure of the gastric proton pump

2019 ◽  
Author(s):  
Kenta Yamamoto ◽  
Vikas Dubey ◽  
Katsumasa Irie ◽  
Hanayo Nakanishi ◽  
Himanshu Khandelia ◽  
...  
Keyword(s):  
Binding Site ◽  
Proton Pump ◽  
Atp Hydrolysis ◽  
Energy Requirement ◽  
Cation Binding ◽  
Structural Basis ◽  
Cation Binding Site ◽  
Gastric Proton Pump ◽  
Dynamics Simulations ◽  
P Type

AbstractThe gastric proton pump (H+,K+-ATPase), a P-type ATPase responsible for gastric acidification, mediates electro-neutral exchange of H+ and K+ coupled with ATP hydrolysis, but with an as yet undetermined transport stoichiometry. Here we show crystal structures at a resolution of 2.5 Å of the pump in the E2-P transition state, in which the counter-transporting cation is occluded. We found a single K+ bound to the cation-binding site of H+,K+-ATPase, indicating an exchange of 1H+/1K+ per hydrolysis of one ATP molecule. This fulfils the energy requirement for the generation of a six pH unit gradient across the membrane. The structural basis of K+recognition is resolved, supported by molecular dynamics simulations, and this establishes how H+,K+-ATPase overcomes the energetic challenge to generate an H+ gradient of more than a million-fold – the highest cation gradient known in any mammalian tissue – across the membrane.

scholarly journals Author response: A single K+-binding site in the crystal structure of the gastric proton pump

2019 ◽  
Author(s):  
Kenta Yamamoto ◽  
Vikas Dubey ◽  
Katsumasa Irie ◽  
Hanayo Nakanishi ◽  
Himanshu Khandelia ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Proton Pump ◽  
Author Response ◽  
Gastric Proton Pump

scholarly journals A single K+-binding site in the crystal structure of the gastric proton pump

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kenta Yamamoto ◽  
Vikas Dubey ◽  
Katsumasa Irie ◽  
Hanayo Nakanishi ◽  
Himanshu Khandelia ◽  
...  
Keyword(s):  
Binding Site ◽  
Proton Pump ◽  
Atp Hydrolysis ◽  
Energy Requirement ◽  
Cation Binding ◽  
Structural Basis ◽  
Cation Binding Site ◽  
Gastric Proton Pump ◽  
Dynamics Simulations ◽  
P Type

The gastric proton pump (H+,K+-ATPase), a P-type ATPase responsible for gastric acidification, mediates electro-neutral exchange of H+ and K+ coupled with ATP hydrolysis, but with an as yet undetermined transport stoichiometry. Here we show crystal structures at a resolution of 2.5 Å of the pump in the E2-P transition state, in which the counter-transporting cation is occluded. We found a single K+ bound to the cation-binding site of the H+,K+-ATPase, indicating an exchange of 1H+/1K+ per hydrolysis of one ATP molecule. This fulfills the energy requirement for the generation of a six pH unit gradient across the membrane. The structural basis of K+ recognition is resolved and supported by molecular dynamics simulations, establishing how the H+,K+-ATPase overcomes the energetic challenge to generate an H+ gradient of more than a million-fold—one of the highest cation gradients known in mammalian tissue—across the membrane.

Photophysical Characterisation, Metal Ion Binding and Enantiomeric Recognition of Chiral Ligands Containing Phenazine Fluorophore

2004 ◽  
Vol 69 (4) ◽  
pp. 885-896 ◽  
Author(s):  
Luisa Stella Dolci ◽  
Péter Huszthy ◽  
Erika Samu ◽  
Marco Montalti ◽  
Luca Prodi ◽  
...  
Keyword(s):  
Metal Ion ◽  
Photophysical Properties ◽  
Ion Binding ◽  
Metal Ion Binding ◽  
Ammonium Ions ◽  
Enantiomerically Pure ◽  
Binding Process ◽  
High Affinity ◽  
Enantiomeric Recognition ◽  
Chiral Species

Enantiomerically pure dimethyl- and diisobutyl-substituted phenazino-18-crown-6 ligands bind metal and ammonium ions and also primary aralkylammonium perchlorates in acetonitrile with high affinity, causing pronounced changes in their luminescence properties. In addition, they show enantioselectivity towards chiral primary aralkylammonium perchlorates. The possibility to monitor the binding process by photoluminescence spectroscopy can gain ground for the design of very efficient enantioselective chemosensors for chiral species. The observed changes in the photophysical properties are also an important tool for understanding the interactions present in the adduct.

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