PDBsum entry 1hug

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Lyase(oxo-acid) PDB id
Protein chain
256 a.a. *
AUC ×4
Waters ×231
* Residue conservation analysis
PDB id:
Name: Lyase(oxo-acid)
Title: Differences in anionic inhibition of human carbonic anhydrase i revealed from the structures of iodide and gold cyanide inhibitor complexes
Structure: Carbonic anhydrase i. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
2.00Å     R-factor:   0.171    
Authors: V.Kumar,K.K.Kannan
Key ref:
V.Kumar et al. (1994). Differences in anionic inhibition of human carbonic anhydrase I revealed from the structures of iodide and gold cyanide inhibitor complexes. Acta Crystallogr D Biol Crystallogr, 50, 731-738. PubMed id: 15299369 DOI: 10.1107/S0907444994001873
28-Oct-93     Release date:   30-Apr-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00915  (CAH1_HUMAN) -  Carbonic anhydrase 1
261 a.a.
256 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
= CO(2)
+ 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     cytoplasm   3 terms 
  Biological process     small molecule metabolic process   3 terms 
  Biochemical function     lyase activity     4 terms  


    Added reference    
DOI no: 10.1107/S0907444994001873 Acta Crystallogr D Biol Crystallogr 50:731-738 (1994)
PubMed id: 15299369  
Differences in anionic inhibition of human carbonic anhydrase I revealed from the structures of iodide and gold cyanide inhibitor complexes.
V.Kumar, K.K.Kannan, P.Sathyamurthi.
The crystal structures of two anionic inhibitor complexes of human carbonic anhydrase I (HCAI), namely, HCAI-iodide and HCAI-Au(CN)(2)(-), have been refined by the restrained least-squares method at 2.2 and 2 A nominal resolution, respectively, with good stereochemistry for the final models. The R values have improved from 30.3 to 16.6% for HCAI-iodide and from 28.8 to 17.1% for HCAI-Au(CN)(2)(-). The sites of inhibitor binding as elucidated are totally different in the two structures. The iodide anion replaces the zinc-bound H(2)O/OH(-) ligand and renders the enzyme inactive. This result confirms that the zinc-bound H(2)O/OH(-) is the activity-linked group in carbonic anhydrase enzymes. Au(CN)(2)(-) binds at a different and new site near the zinc ion, without liganding to the metal. The N atom of Au(CN)(2)(-) is within hydrogen-bonding distance of the zinc-bound H(2)O/OH(-) group which shifts by about 0.4 A away from the zinc ion in relation to its position in the native HCAI. It is proposed that the presence of the inhibitor Au(CN)(2)(-) results in a conformational reorientation of the activity-linked group, due to hydrogen-bond formation with the inhibitor, which in turn sterically hinders the binding of the substrate CO(2) molecule in the active site, leading to the inhibition of HCAI enzyme.
  Selected figure(s)  
Figure 3.
Fig. 3. Electron density in the (Fo- Fc) 'omit' map for the active-site Au(CN)2 anion and the activity-linked H20/OH- group in HCAI-Au(CN)z-. Contours are drawn at the +40" level.
Figure 4.
Fig. 4. The active site in HCAI enzyme. Also shown are binding sites of inhibitors I and Au(CN)2 .
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1994, 50, 731-738) copyright 1994.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20118557 A.Sugimoto, H.Ikeda, H.Tsukamoto, K.Kihira, M.Ishioka, J.Hirose, T.Hata, H.Fujioka, and Y.Ono (2010).
Timolol Activates the Enzyme Activities of Human Carbonic Anhydrase I and II.
  Biol Pharm Bull, 33, 301-306.  
20505865 V.Alterio, S.M.Monti, E.Truppo, C.Pedone, C.T.Supuran, and G.De Simone (2010).
The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex.
  Org Biomol Chem, 8, 3528-3533.
PDB code: 3lxe
18451496 A.Sugimoto, H.Ikeda, H.Tsukamoto, K.Kihira, C.Takeda, J.Hirose, T.Hata, E.Baba, and Y.Ono (2008).
The mechanisms by which latanoprost free acid inhibits human carbonic anhydrase I and II.
  Biol Pharm Bull, 31, 796-801.  
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.  
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