2cbc
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2cbc.jpg|left|200px]] | [[Image:2cbc.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2cbc", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_2cbc| PDB=2cbc | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''STRUCTURE OF NATIVE AND APO CARBONIC ANHYDRASE II AND SOME OF ITS ANION-LIGAND COMPLEXES''' | '''STRUCTURE OF NATIVE AND APO CARBONIC ANHYDRASE II AND SOME OF ITS ANION-LIGAND COMPLEXES''' | ||
| Line 30: | Line 27: | ||
[[Category: Liljas, A.]] | [[Category: Liljas, A.]] | ||
[[Category: Svensson, L A.]] | [[Category: Svensson, L A.]] | ||
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:38:54 2008'' | |
| - | + | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 18:38, 3 May 2008
STRUCTURE OF NATIVE AND APO CARBONIC ANHYDRASE II AND SOME OF ITS ANION-LIGAND COMPLEXES
Overview
In order to obtain a better structural framework for understanding the catalytic mechanism of carbonic anhydrase, a number of inhibitor complexes of the enzyme were investigated crystallographically. The three-dimensional structure of free human carbonic anhydrase II was refined at pH 7.8 (1.54 A resolution) and at pH 6.0 (1.67 A resolution). The structure around the zinc ion was identical at both pH values. The structure of the zinc-free enzyme was virtually identical with that of the native enzyme, apart from a water molecule that had moved 0.9 A to fill the space that would be occupied by the zinc ion. The complexes with the anionic inhibitors bisulfite and formate were also studied at neutral pH. Bisulfite binds with one of its oxygen atoms, presumably protonized, to the zinc ion and replaces the zinc water. Formate, lacking a hydroxyl group, is bound with its oxygen atoms not far away from the position of the non-protonized oxygen atoms of the bisulfite complex, i.e. at hydrogen bond distance from Thr199 N and at a position between the zinc ion and the hydrophobic part of the active site. The result of these and other studies have implications for our view of the catalytic function of the enzyme, since virtually all inhibitors share some features with substrate, product or expected transition states. A reaction scheme where electrophilic activation of carbon dioxide plays an important role in the hydration reaction is presented. In the reverse direction, the protonized oxygen of the bicarbonate is forced upon the zinc ion, thereby facilitating cleavage of the carbon-oxygen bond. This is achieved by the combined action of the anionic binding site, which binds carboxyl groups, the side-chain of threonine 199, which discriminates between hydrogen bond donors and acceptors, and hydrophobic interaction between substrate and the active site cavity. The required proton transfer between the zinc water and His64 can take place through water molecules 292 and 318.
About this Structure
2CBC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of native and apo carbonic anhydrase II and structure of some of its anion-ligand complexes., Hakansson K, Carlsson M, Svensson LA, Liljas A, J Mol Biol. 1992 Oct 20;227(4):1192-204. PMID:1433293 Page seeded by OCA on Sat May 3 21:38:54 2008
