PDBsum entry 1caj

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Lyase(oxo-acid) PDB id
Protein chain
258 a.a. *
Waters ×208
* Residue conservation analysis
PDB id:
Name: Lyase(oxo-acid)
Title: Structural analysis of the zinc hydroxide-thr 199-glu 106 hydrogen bonding network in human carbonic anhydrase ii
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
1.90Å     R-factor:   0.151    
Authors: Y.Xue,A.Liljas,B.-H.Jonsson,S.Lindskog
Key ref: Y.Xue et al. (1993). Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II. Proteins, 17, 93. PubMed id: 7901850
17-Sep-92     Release date:   31-Oct-93    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
260 a.a.
258 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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     extracellular space   11 terms 
  Biological process     angiotensin-mediated signaling pathway   21 terms 
  Biochemical function     protein binding     5 terms  


    Added reference    
Proteins 17:93 (1993)
PubMed id: 7901850  
Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II.
Y.Xue, A.Liljas, B.H.Jonsson, S.Lindskog.
The significance of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in the active site of human carbonic anhydrase II has been examined by X-ray crystallographic analyses of site-specific mutants. Mutants with Ala-199 and Ala-106 or Gln-106 have low catalytic activities, while a mutant with Asp-106 has almost full CO2 hydration activity. The structures of these four mutants, as well as that of the bicarbonate complex of the mutant with Ala-199, have been determined at 1.7 to 2.2 A resolution. Removal of the gamma atoms of residue 199 leads to a distorted tetrahedral geometry at the zinc ion, and a catalytically important zinc-bound water molecule has moved towards Glu-106. In the bicarbonate complex of the mutant with Ala-199 one oxygen atom from bicarbonate binds to zinc without displacing this water molecule. Tetrahedral coordination geometries are retained in the mutants at position 106. The mutants with Ala-106 and Gln-106 have a zinc-bound sulfate ion, whereas this sulfate site is only partially occupied in the mutant with Asp-106. The hydrogen-bond network seems to be "reversed" in the mutants with Ala-106 and Gln-106. The network is preserved as in native enzyme in the mutant with Asp-106 but the side chain of Asp-106 is more extended than that of Glu-106 in the native enzyme. These results illustrate the importance of Glu-106 and Thr-199 for controlling the precise coordination geometry of the zinc ion and its ligand preferences which results in an optimal orientation of a zinc-bound hydroxide ion for an attack on the CO2 substrate.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21377464 J.A.Cuesta-Seijo, M.S.Borchert, J.C.Navarro-Poulsen, K.M.Schnorr, S.B.Mortensen, and L.Lo Leggio (2011).
Structure of a dimeric fungal α-type carbonic anhydrase.
  FEBS Lett, 585, 1042-1048.  
19520834 B.Sjöblom, M.Polentarutti, and K.Djinovic-Carugo (2009).
Structural study of X-ray induced activation of carbonic anhydrase.
  Proc Natl Acad Sci U S A, 106, 10609-10613.
PDB codes: 2vva 2vvb
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.  
14660577 D.A.Whittington, J.H.Grubb, A.Waheed, G.N.Shah, W.S.Sly, and D.W.Christianson (2004).
Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes.
  J Biol Chem, 279, 7223-7228.
PDB codes: 1rj5 1rj6
12107142 K.S.Smith, C.Ingram-Smith, and J.G.Ferry (2002).
Roles of the conserved aspartate and arginine in the catalytic mechanism of an archaeal beta-class carbonic anhydrase.
  J Bacteriol, 184, 4240-4245.  
12056894 S.Huang, B.Sjöblom, A.E.Sauer-Eriksson, and B.H.Jonsson (2002).
Organization of an efficient carbonic anhydrase: implications for the mechanism based on structure-function studies of a T199P/C206S mutant.
  Biochemistry, 41, 7628-7635.
PDB codes: 1lg5 1lg6 1lgd
10978542 K.S.Smith, and J.G.Ferry (2000).
Prokaryotic carbonic anhydrases.
  FEMS Microbiol Rev, 24, 335-366.  
9653544 H.H.Thorp (1998).
Bioinorganic chemistry and drug design: here comes zinc again.
  Chem Biol, 5, R125-R127.  
9336012 S.Lindskog (1997).
Structure and mechanism of carbonic anhydrase.
  Pharmacol Ther, 74, 1.  
  8665839 C.Kisker, H.Schindelin, B.E.Alber, J.G.Ferry, and D.C.Rees (1996).
A left-hand beta-helix revealed by the crystal structure of a carbonic anhydrase from the archaeon Methanosarcina thermophila.
  EMBO J, 15, 2323-2330.
PDB code: 1thj
8539245 R.H.Stote, and M.Karplus (1995).
Zinc binding in proteins and solution: a simple but accurate nonbonded representation.
  Proteins, 23, 12-31.  
8306976 A.Liljas, K.Håkansson, B.H.Jonsson, and Y.Xue (1994).
Inhibition and catalysis of carbonic anhydrase. Recent crystallographic analyses.
  Eur J Biochem, 219, 1.  
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