scholarly journals Neutron Structure of Human Carbonic Anhydrase II: A Hydrogen-Bonded Water Network “Switch” Is Observed between pH 7.8 and 10.0

Biochemistry ◽  
2011 ◽  
Vol 50 (44) ◽  
pp. 9421-9423 ◽  
Author(s):  
Zoë Fisher ◽  
Andrey Y. Kovalevsky ◽  
Marat Mustyakimov ◽  
David N. Silverman ◽  
Robert McKenna ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Water Network ◽  
Neutron Structure ◽  
Human Carbonic Anhydrase ◽  
Network Switch ◽  
Hydrogen Bonded

scholarly journals Active-site solvent replenishment observed during human carbonic anhydrase II catalysis

IUCrJ ◽  
2018 ◽  
Vol 5 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Jin Kyun Kim ◽  
Carrie L. Lomelino ◽  
Balendu Sankara Avvaru ◽  
Brian P. Mahon ◽  
Robert McKenna ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Proton Transfer ◽  
Active Site ◽  
Water Reservoir ◽  
Bound Water ◽  
Nucleophilic Attack ◽  
Carbonic Anhydrase Ii ◽  
Intermediate Water ◽  
Water Network ◽  
Human Carbonic Anhydrase

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO2/HCO3 −. Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (WI′) is observed next to the previously observed intermediate water WI, and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH− on CO2. This mechanism explains how the zinc-bound water (WZn) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first `physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.

scholarly journals Neutron Structure of Human Carbonic Anhydrase II: Implications for Proton Transfer

Biochemistry ◽  
2010 ◽  
Vol 49 (3) ◽  
pp. 415-421 ◽  
Author(s):  
S. Zoë Fisher ◽  
Andrey Y. Kovalevsky ◽  
John F. Domsic ◽  
Marat Mustyakimov ◽  
Robert McKenna ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Proton Transfer ◽  
Carbonic Anhydrase Ii ◽  
Neutron Structure ◽  
Human Carbonic Anhydrase

scholarly journals The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 509 ◽  
Author(s):  
Steffen Glöckner ◽  
Khang Ngo ◽  
Björn Wagner ◽  
Andreas Heine ◽  
Gerhard Klebe
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
The Novel ◽  
Binding Modes ◽  
X Ray ◽  
Structure Activity ◽  
Small Set ◽  
Novel Method ◽  
Human Carbonic Anhydrase ◽  
Kinetics Of

The fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.

Salt mediated unusual switching in the aggregation kinetic profile of human carbonic anhydrase

RSC Advances ◽  
2015 ◽  
Vol 5 (116) ◽  
pp. 95717-95726 ◽  
Author(s):  
Preeti Gupta ◽  
Shashank Deep
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Aggregation Kinetic ◽  
Kinetic Profile ◽  
Human Carbonic Anhydrase

Aggregation pathway of human carbonic anhydrase II in the presence of salt.

Electron spin echo decay as a probe of aminoxyl environment in spin-labeled mutants of human carbonic anhydrase II †

1997 ◽  
pp. 2549-2554 ◽  
Author(s):  
Mikael Lindgren ◽  
Gareth R. Eaton ◽  
Sandra S. Eaton ◽  
Bengt-Harald Jonsson ◽  
Per Hammarström ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Electron Spin ◽  
Spin Echo ◽  
Electron Spin Echo ◽  
Carbonic Anhydrase Ii ◽  
Human Carbonic Anhydrase
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