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| - | [[Image:1bv3.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1bv3.png|left|200px]] |
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| | {{STRUCTURE_1bv3| PDB=1bv3 | SCENE= }} | | {{STRUCTURE_1bv3| PDB=1bv3 | SCENE= }} |
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| - | '''HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH UREA'''
| + | ===HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH UREA=== |
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| - | ==Overview==
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| - | The interaction of human carbonic anhydrase (hCA) isozymes I and II with cyanamide, a linear molecule isoelectronic with the main physiological substrate of the enzyme, CO(2), was investigated through spectroscopic, kinetic, and X-ray crystallographic studies. We show here that cyanamide is hydrated to urea in the presence of CAs, and that it also acts as a weak non-competitive inhibitor (K(I)=61+/-3 mM and 238+/-9 mM for hCA II and hCA I, respectively) towards the esterasic activity of these enzymes, as tested with 4-nitrophenyl acetate. Changes in the spectrum of the Co(II)-hCA II derivative observed in the presence of cyanamide suggest that it likely binds the metal ion within the CA active site, adding to the coordination sphere, not substituting the metal-bound solvent molecule. It thereafter undergoes a nucleophilic attack from the metal-bound hydroxide ion, forming urea which remains bound to the metal, as observed in the X-ray crystal structure of hCA II soaked in cyanamide solutions for several hours. The urea molecule is directly coordinated to the active site Zn(II) ion through a protonated nitrogen atom. Several hydrogen bonds involving active site residues Thr199 and Thr200 as well as three water molecules (Wat99, Wat122, and Wat123) further stabilize the urea-hCA II adduct. Kinetic studies in solution further proved that urea acts as a tight binding inhibitor of the two isozymes hCA I and hCA II, with very slow binding kinetics (k(on) = 2.5 x 10(-5)s(-1)M(-1)). A mechanism to explain the hydration process of cyanamide by CAs, as well as the tight binding of urea in the active site, is also proposed based on the hypothesis that urea is deprotonated when bound to the enzyme. Cyanamide is thus the first true suicide substrate of this enzyme for which binding has been documented by means of X-ray crystallographic and spectroscopic studies. | + | The line below this paragraph, {{ABSTRACT_PUBMED_10550681}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10550681 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10550681}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Vernaglione, G.]] | | [[Category: Vernaglione, G.]] |
| | [[Category: Carbonate hydro-lyase]] | | [[Category: Carbonate hydro-lyase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:59:19 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:45:59 2008'' |
Revision as of 16:46, 30 June 2008
Template:STRUCTURE 1bv3
HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH UREA
Template:ABSTRACT PUBMED 10550681
About this Structure
1BV3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction?, Briganti F, Mangani S, Scozzafava A, Vernaglione G, Supuran CT, J Biol Inorg Chem. 1999 Oct;4(5):528-36. PMID:10550681
Page seeded by OCA on Mon Jun 30 19:45:59 2008
