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PDBsum entry 1caj

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protein ligands metals links
Lyase(oxo-acid) PDB id
1caj
Jmol
Contents
Protein chain
258 a.a. *
Ligands
SO4
Metals
_ZN
Waters ×208
* Residue conservation analysis
PDB id:
1caj
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
Resolution:
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
Date:
17-Sep-92     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
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.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     extracellular space   10 terms 
  Biological process     angiotensin-mediated signaling pathway   19 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.
 
  ABSTRACT  
 
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.  
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 codes are shown on the right.