A Novel Carbonic Anhydrase II Binding Site Regulates NHE1 Activity†

Biochemistry ◽  
2006 ◽  
Vol 45 (7) ◽  
pp. 2414-2424 ◽  
Author(s):  
Xiuju Li ◽  
Yongsheng Liu ◽  
Bernardo V. Alvarez ◽  
Joseph R. Casey ◽  
Larry Fliegel
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Carbonic Anhydrase Ii ◽  
Nhe1 Activity

Effect of the hydrogen bond network in carbonic anhydrase II zinc binding site. A theoretical study

1998 ◽  
Vol 76 (7) ◽  
pp. 1027-1032 ◽  
Author(s):  
Silvia Álvarez-Santos ◽  
Àngels González-Lafont ◽  
José M Lluch
Keyword(s):  
Hydrogen Bond ◽  
Carbonic Anhydrase ◽  
Binding Site ◽  
Zinc Binding ◽  
Carbonic Anhydrase Ii ◽  
Am1 Method ◽  
Hydrogen Bond Network ◽  
Zinc Binding Site ◽  
Bond Network ◽  
Metal Ligand

The hydrogen bond network influence on the carbonic anhydrase II (CAII) zinc binding site has been studied theoretically by using the semiempirical AM1 method. To this aim, quantum mechanical reduced models of wild-type CAII and several CAII variants have been constructed. We have shown that, when a direct metal ligand donates a hydrogen bond to an indirect metal ligand, the first-shell residues enhance their electrostatic interaction with the zinc cation. Thus, the hydrogen-bond network is able to modulate the zinc binding affinity and the zinc-water pKa.Key words: hydrogen bond network, carbonic anhydrase II, Zn2+ metalloenzyme ligands.

Engineering a cysteine ligand into the zinc binding site of human carbonic anhydrase II

Biochemistry ◽  
1993 ◽  
Vol 32 (38) ◽  
pp. 9896-9900 ◽  
Author(s):  
Laura L. Kiefer ◽  
Joseph F. Krebs ◽  
Steven A. Paterno ◽  
Carol A. Fierke
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Zinc Binding ◽  
Carbonic Anhydrase Ii ◽  
Zinc Binding Site ◽  
Human Carbonic Anhydrase

Localization of the Cl-/HCO3-Anion Exchanger Binding Site to the Amino-Terminal Region of Carbonic Anhydrase II†

Biochemistry ◽  
2000 ◽  
Vol 39 (44) ◽  
pp. 13344-13349 ◽  
Author(s):  
John W. Vince ◽  
Uno Carlsson ◽  
Reinhart A. F. Reithmeier
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Anion Exchanger ◽  
Terminal Region ◽  
Carbonic Anhydrase Ii ◽  
Amino Terminal

Identification of the Carbonic Anhydrase II Binding Site in the Cl-/HCO3-Anion Exchanger AE1†

Biochemistry ◽  
2000 ◽  
Vol 39 (18) ◽  
pp. 5527-5533 ◽  
Author(s):  
John W. Vince ◽  
Reinhart A. F. Reithmeier
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Anion Exchanger ◽  
Carbonic Anhydrase Ii

Structures of Human Carbonic Anhydrase II/Inhibitor Complexes Reveal a Second Binding Site for Steroidal and Nonsteroidal Inhibitors,

Biochemistry ◽  
2010 ◽  
Vol 49 (16) ◽  
pp. 3464-3476 ◽  
Author(s):  
Gyles E. Cozier ◽  
Mathew P. Leese ◽  
Matthew D. Lloyd ◽  
Matthew D. Baker ◽  
Nethaji Thiyagarajan ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Carbonic Anhydrase Ii ◽  
Human Carbonic Anhydrase

scholarly journals Human carbonic anhydrase II–cyanate inhibitor complex: putting the debate to rest

2014 ◽  
Vol 70 (10) ◽  
pp. 1324-1327 ◽  
Author(s):  
Dayne West ◽  
Melissa A. Pinard ◽  
Chingkuang Tu ◽  
David N. Silverman ◽  
Robert McKenna
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Solvent Molecule ◽  
Carbonic Anhydrase Ii ◽  
Binding Modes ◽  
Wild Type ◽  
X Ray ◽  
Exchange Mass Spectrometry ◽  
Close Proximity ◽  
A Site

The binding of anions to carbonic anhydrase II (CA II) has been attributed to high affinity for the active-site zinc. An anion of interest is cyanate, for which contrasting binding modes have been reported in the literature. Previous spectroscopic data have shown cyanate behaving as an inhibitor, directly binding to the zinc, in contrast to previous crystallographic data that implied that cyanate acts as a substrate mimic that is not directly bound to the zinc but overlaps with the binding site of the substrate CO2. Wild-type and the V207I variant of CA II have been expressed and X-ray crystal structures of their cyanate complexes have been determined to 1.7 and 1.5 Å resolution, respectively. The rationale for the V207I CA II variant was its close proximity to the CO2-binding site. Both structures clearly show that the cyanate binds directly to the zinc. In addition, inhibition constants (∼40 µM) were measured using18O-exchange mass spectrometry for wild-type and V207I CA II and were similar to those determined previously (Supuranet al., 1997). Hence, it is concluded that under the conditions of these experiments the binding of cyanate to CA II is directly to the zinc, displacing the zinc-bound solvent molecule, and not in a site that overlaps with the CO2substrate-binding site.

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