PDBsum entry 1bv3

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protein ligands metals links
Lyase PDB id
Protein chain
257 a.a. *
Waters ×134
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Human carbonic anhydrase ii complexed with urea
Structure: Protein (carbonic anhydrase ii). Chain: a. Synonym: hca ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: erythrocytes. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.85Å     R-factor:   0.171     R-free:   0.213
Authors: F.Briganti,S.Mangani,A.Scozzafava,G.Vernaglione,C.T.Supuran
Key ref: F.Briganti et al. (1999). Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction? J Biol Inorg Chem, 4, 528-536. PubMed id: 10550681
22-Sep-98     Release date:   28-Sep-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
260 a.a.
257 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
Bound ligand (Het Group name = URE)
matches with 40.00% similarity
+ H(2)O
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   11 terms 
  Biological process     angiotensin-mediated signaling pathway   21 terms 
  Biochemical function     protein binding     5 terms  


    Added reference    
J Biol Inorg Chem 4:528-536 (1999)
PubMed id: 10550681  
Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction?
F.Briganti, S.Mangani, A.Scozzafava, G.Vernaglione, C.T.Supuran.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
18335973 V.M.Krishnamurthy, G.K.Kaufman, A.R.Urbach, I.Gitlin, K.L.Gudiksen, D.B.Weibel, and G.M.Whitesides (2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.
  Chem Rev, 108, 946.  
12500287 C.T.Supuran, A.Scozzafava, and A.Casini (2003).
Carbonic anhydrase inhibitors.
  Med Res Rev, 23, 146-189.  
11015219 A.Guerri, F.Briganti, A.Scozzafava, C.T.Supuran, and S.Mangani (2000).
Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction.
  Biochemistry, 39, 12391-12397.
PDB code: 1f2w
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