scholarly journals Effect of Active-site Mutation at Asn67 on the Proton Transfer Mechanism of Human Carbonic Anhydrase II

Biochemistry ◽  
2009 ◽  
Vol 48 (33) ◽  
pp. 7996-8005 ◽  
Author(s):  
C. Mark Maupin ◽  
Jiayin Zheng ◽  
Chingkuang Tu ◽  
Robert McKenna ◽  
David N. Silverman ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Proton Transfer ◽  
Active Site ◽  
Transfer Mechanism ◽  
Carbonic Anhydrase Ii ◽  
Site Mutation ◽  
Human Carbonic Anhydrase

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 Structural and Kinetic Study of the Extended Active Site for Proton Transfer in Human Carbonic Anhydrase II

Biochemistry ◽  
2010 ◽  
Vol 49 (30) ◽  
pp. 6394-6399 ◽  
Author(s):  
John F. Domsic ◽  
Wilton Williams ◽  
Suzanne Z. Fisher ◽  
Chingkuang Tu ◽  
Mavis Agbandje-McKenna ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Proton Transfer ◽  
Kinetic Study ◽  
Active Site ◽  
Carbonic Anhydrase Ii ◽  
Human Carbonic Anhydrase

Atomic Crystal and Molecular Dynamics Simulation Structures of Human Carbonic Anhydrase II:  Insights into the Proton Transfer Mechanism†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (11) ◽  
pp. 2930-2937 ◽  
Author(s):  
S. Zoë Fisher ◽  
C. Mark Maupin ◽  
Monika Budayova-Spano ◽  
Lakshmanan Govindasamy ◽  
Chingkuang Tu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Carbonic Anhydrase ◽  
Proton Transfer ◽  
Transfer Mechanism ◽  
Dynamics Simulation ◽  
Carbonic Anhydrase Ii ◽  
Human Carbonic Anhydrase ◽  
Atomic Crystal

scholarly journals Water Networks in Fast Proton Transfer during Catalysis by Human Carbonic Anhydrase II

Biochemistry ◽  
2012 ◽  
Vol 52 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Rose Mikulski ◽  
Dayne West ◽  
Katherine H. Sippel ◽  
Balendu Sankara Avvaru ◽  
Mayank Aggarwal ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Proton Transfer ◽  
Carbonic Anhydrase Ii ◽  
Water Networks ◽  
Fast Proton ◽  
Human Carbonic Anhydrase

Out of the active site binding pocket for carbonic anhydrase inhibitors

2015 ◽  
Vol 51 (2) ◽  
pp. 302-305 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Simone Carradori ◽  
Simona M. Monti ◽  
Martina Buonanno ◽  
Daniela Secci ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Binding Pocket ◽  
Carbonic Anhydrase Ii ◽  
Carbonic Anhydrase Inhibitors ◽  
Human Carbonic Anhydrase ◽  
Site Binding

2-Benzylsulfinylbenzoic acid binds to human carbonic anhydrase II in a mode completely different from any other class of carbonic anhydrase inhibitors investigated so far.

Sign in / Sign up

Export Citation Format

Share Document