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PDBsum entry 2fw4

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protein ligands metals links
Lyase PDB id
2fw4
Jmol
Contents
Protein chains
257 a.a. *
Ligands
HIS ×2
Metals
_ZN ×2
Waters ×370
* Residue conservation analysis
PDB id:
2fw4
Name: Lyase
Title: Carbonic anhydrase activators. The first x-ray crystallographic study of an activator of isoform i, structure with l-histidine.
Structure: Carbonic anhydrase 1. Chain: a, b. Synonym: carbonic anhydrase i, carbonate dehydratase i, ca- i. Ec: 4.2.1.1
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.00Å     R-factor:   0.217     R-free:   0.303
Authors: C.Temperini,A.Scozzafava,C.T.Supuran
Key ref: C.Temperini et al. (2006). Carbonic anhydrase activators: the first X-ray crystallographic study of an adduct of isoform I. Bioorg Med Chem Lett, 16, 5152-5156. PubMed id: 16870440 DOI: 10.1016/j.bmcl.2006.07.021
Date:
01-Feb-06     Release date:   08-Aug-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00915  (CAH1_HUMAN) -  Carbonic anhydrase 1
Seq:
Struc:
261 a.a.
257 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.1  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
H(2)CO(3)
= CO(2)
+ H(2)O
      Cofactor: Zinc
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: 10.1016/j.bmcl.2006.07.021 Bioorg Med Chem Lett 16:5152-5156 (2006)
PubMed id: 16870440  
 
 
Carbonic anhydrase activators: the first X-ray crystallographic study of an adduct of isoform I.
C.Temperini, A.Scozzafava, C.T.Supuran.
 
  ABSTRACT  
 
The X-ray crystallographic structure for the adduct of an activator with human carbonic anhydrase isozyme I (hCA I) is reported. L-Histidine binds deep within the enzyme active site, participating in a network of hydrogen bonds involving its carboxylate moiety and the zinc-bound water molecule, as well as the imidazole of His200, being in van der Waals contacts with Thr199, His200, His64, and His67. This binding is very different from that to the other major cytosolic isozyme hCA II.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21369613 K.Dave, A.Scozzafava, D.Vullo, C.T.Supuran, and M.A.Ilies (2011).
Pyridinium derivatives of histamine are potent activators of cytosolic carbonic anhydrase isoforms I, II and VII.
  Org Biomol Chem, 9, 2790-2800.  
21036610 K.Dave, M.A.Ilies, A.Scozzafava, C.Temperini, D.Vullo, and C.T.Supuran (2011).
An inhibitor-like binding mode of a carbonic anhydrase activator within the active site of isoform II.
  Bioorg Med Chem Lett, 21, 2764-2768.  
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
18167490 C.T.Supuran (2008).
Carbonic anhydrases: novel therapeutic applications for inhibitors and activators.
  Nat Rev Drug Discov, 7, 168-181.  
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.  
17499996 I.Nishimori, S.Onishi, D.Vullo, A.Innocenti, A.Scozzafava, and C.T.Supuran (2007).
Carbonic anhydrase activators: the first activation study of the human secretory isoform VI with amino acids and amines.
  Bioorg Med Chem, 15, 5351-5357.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.