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PDBsum entry 2ca2
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protein ligands metals links
Lyase(oxo-acid) PDB id
2ca2

 

 

 

 

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Contents
Protein chain
256 a.a. *
Ligands
SCN
Metals
_ZN
_HG
Waters ×172
* Residue conservation analysis
PDB id:
2ca2
Name: Lyase(oxo-acid)
Title: Crystallographic studies of inhibitor binding sites in human carbonic anhydrase ii. A pentacoordinated binding of the scn-ion to the zinc at high p H
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.90Å     R-factor:   0.176    
Authors: A.E.Eriksson,P.M.Kylsten,T.A.Jones,A.Liljas
Key ref: A.E.Eriksson et al. (1988). Crystallographic studies of inhibitor binding sites in human carbonic anhydrase II: a pentacoordinated binding of the SCN- ion to the zinc at high pH. Proteins, 4, 283-293. PubMed id: 3151020
Date:
06-Feb-89     Release date:   15-Jan-90    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens
Seq:
Struc: 		260 a.a.
256 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.4.2.1.1  - carbonic anhydrase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: hydrogencarbonate + H+ = CO2 + H2O
hydrogencarbonate
 + H(+)
 = CO2
 + H2O
      Cofactor: Zn(2+)
   Enzyme class 3: E.C.4.2.1.69  - cyanamide hydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: urea = cyanamide + H2O
urea
 =
cyanamide
Bound ligand (Het Group name = SCN)
matches with 50.00% similarity 		+ H2O
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Proteins 4:283-293 (1988)
PubMed id: 3151020  
 
 
Crystallographic studies of inhibitor binding sites in human carbonic anhydrase II: a pentacoordinated binding of the SCN- ion to the zinc at high pH.
A.E.Eriksson, P.M.Kylsten, T.A.Jones, A.Liljas.
 
  ABSTRACT  
 
The binding of four inhibitors--mercuric ion, 3-acetoxymercuri-4-aminobenzenesulfonamide (AMS), acetazolamide (Diamox), and thiocyanate ion--to human carbonic anhydrase II (HCA II) has been studied with X-ray crystallography. The binding of mercury to HCA II at pH 7.0 has been investigated at 3.1 A resolution. Mercuric ions are observed at both nitrogens in the His-64 ring. One of these sites is pointing toward the zinc ion. The only other binding site for mercury is at Cys-206. The binding of the two sulfonamide inhibitors AMS and Diamox, has been reinvestigated at 2.0 and 3.0 A, respectively. Only the nitrogen of the sulfonamide group binds to the zinc ion replacing the hydroxyl ion. The sulfonamide oxygen closest to the zinc ion is 3.1 A away. Thus the tetrahedral geometry of the zinc is retained, refuting earlier models of a pentacoordinated zinc. The structure of the thiocyanate complex has been investigated at pH 8.5 and the structure has been refined at 1.9 A resolution using the least-squares refinement program PROLSQ. The crystallographic R factor is 17.6%. The zinc ion is pentacoordinated with the anion as well as a water molecule bound in addition to the three histidine residues. The nitrogen atom of the SCN- ion is 1.9 A from the zinc ion but shifted 1.3 A with respect to the hydroxyl ion in the native structure and at van der Waals' distance from the O gamma l atom of Thr-199. This is due to the inability of the O gamma l atom of Thr-199 to serve as a hydrogen bond donor, thus repelling the nonprotonated nitrogen. The SCN- molecule reaches into the deep end of the active site cavity where the sulfur atom has displaced the so-called "deep" water molecule of the native enzyme. The zinc-bound water molecule is 2.2 A from the zinc ion and 2.4 A from the SCN- nitrogen. In addition, this water is hydrogen bonded to the O gamma l atom of Thr-199 and to another water molecule. We have observed that solvent and inhibitor molecules have three possible binding sites on the zinc ion and their significance for the catalysis and inhibition of HCA II will be discussed. All available crystallographic data are consistent with a proposed catalytic mechanism in which both the OH moiety and one oxygen of the substrate HCO3- ion are ligated to the zinc ion.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20931644 A.Casini, C.Temperini, C.Gabbiani, C.T.Supuran, and L.Messori (2010).
The x-ray structure of the adduct between NAMI-A and carbonic anhydrase provides insights into the reactivity of this metallodrug with proteins.
  ChemMedChem, 5, 1989-1994.
PDB code: 3m1j
19679198 J.F.Domsic, and R.McKenna (2010).
Sequestration of carbon dioxide by the hydrophobic pocket of the carbonic anhydrases.
  Biochim Biophys Acta, 1804, 326-331.  
19438233 C.M.Maupin, R.McKenna, D.N.Silverman, and G.A.Voth (2009).
Elucidation of the proton transport mechanism in human carbonic anhydrase II.
  J Am Chem Soc, 131, 7598-7608.  
19588465 D.Aili, R.Selegård, L.Baltzer, K.Enander, and B.Liedberg (2009).
Colorimetric protein sensing by controlled assembly of gold nanoparticles functionalized with synthetic receptors.
  Small, 5, 2445-2452.  
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.  
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.  
11073902 K.S.Smith, N.J.Cosper, C.Stalhandske, R.A.Scott, and J.G.Ferry (2000).
Structural and kinetic characterization of an archaeal beta-class carbonic anhydrase.
  J Bacteriol, 182, 6605-6613.  
10354450 J.Gao, Q.Wu, J.Carbeck, Q.P.Lei, R.D.Smith, and G.M.Whitesides (1999).
Probing the energetics of dissociation of carbonic anhydrase-ligand complexes in the gas phase.
  Biophys J, 76, 3253-3260.  
  9541386 T.Stams, Y.Chen, P.A.Boriack-Sjodin, J.D.Hurt, J.Liao, J.A.May, T.Dean, P.Laipis, D.N.Silverman, and D.W.Christianson (1998).
Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination.
  Protein Sci, 7, 556-563.
PDB codes: 1a42 2znc 3znc
9061790 C.T.Supuran, C.W.Conroy, and T.H.Maren (1997).
Is cyanate a carbonic anhydrase substrate?
  Proteins, 27, 272-278.  
9252341 J.A.Hunt, and C.A.Fierke (1997).
Selection of carbonic anhydrase variants displayed on phage. Aromatic residues in zinc binding site enhance metal affinity and equilibration kinetics.
  J Biol Chem, 272, 20364-20372.  
8995407 M.L.Brader, N.C.Kaarsholm, S.E.Harnung, and M.F.Dunn (1997).
Ligand perturbation effects on a pseudotetrahedral Co(II)(His)3-ligand site. A magnetic circular dichroism study of the Co(II)-substituted insulin hexamer.
  J Biol Chem, 272, 1088-1094.  
9263637 O.Braha, B.Walker, S.Cheley, J.J.Kasianowicz, L.Song, J.E.Gouaux, and H.Bayley (1997).
Designed protein pores as components for biosensors.
  Chem Biol, 4, 497-505.  
9336012 S.Lindskog (1997).
Structure and mechanism of carbonic anhydrase.
  Pharmacol Ther, 74, 1.  
8807898 A.M.Schmidt, H.N.Müller, and A.Skerra (1996).
A Zn(II)-binding site engineered into retinol-binding protein exhibits metal-ion specificity and allows highly efficient affinity purification with a newly designed metal ligand.
  Chem Biol, 3, 645-653.  
7597074 J.J.Burbaum, M.H.Ohlmeyer, J.C.Reader, I.Henderson, L.W.Dillard, G.Li, T.L.Randle, N.H.Sigal, D.Chelsky, and J.J.Baldwin (1995).
A paradigm for drug discovery employing encoded combinatorial libraries.
  Proc Natl Acad Sci U S A, 92, 6027-6031.  
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.  
8497481 A.E.Eriksson, and A.Liljas (1993).
Refined structure of bovine carbonic anhydrase III at 2.0 A resolution.
  Proteins, 16, 29-42.  
8441752 M.Lindahl, L.A.Svensson, and A.Liljas (1993).
Metal poison inhibition of carbonic anhydrase.
  Proteins, 15, 177-182.  
8473916 S.H.Rotstein, and M.A.Murcko (1993).
GenStar: a method for de novo drug design.
  J Comput Aided Mol Des, 7, 23-43.  
8477723 S.K.Nair, and D.W.Christianson (1993).
Crystallographic studies of azide binding to human carbonic anhydrase II.
  Eur J Biochem, 213, 507-515.  
7901850 Y.Xue, A.Liljas, B.H.Jonsson, and S.Lindskog (1993).
Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II.
  Proteins, 17, 93.
PDB codes: 1cai 1caj 1cak 1cal 1cam
8451242 Y.Xue, J.Vidgren, L.A.Svensson, A.Liljas, B.H.Jonsson, and S.Lindskog (1993).
Crystallographic analysis of Thr-200-->His human carbonic anhydrase II and its complex with the substrate, HCO3-.
  Proteins, 15, 80-87.
PDB code: 1bic
8265567 Z.Peng, K.M.Merz, and L.Banci (1993).
Binding of cyanide, cyanate, and thiocyanate to human carbonic anhydrase II.
  Proteins, 17, 203-216.  
  1598233 A.Bairoch, and B.Boeckmann (1992).
The SWISS-PROT protein sequence data bank.
  Nucleic Acids Res, 20, 2019-2022.  
1420895 L.Banci, L.B.Dugad, G.N.La Mar, K.A.Keating, C.Luchinat, and R.Pierattelli (1992).
1H nuclear magnetic resonance investigation of cobalt(II) substituted carbonic anhydrase.
  Biophys J, 63, 530-543.  
1336460 S.Mangani, and K.Håkansson (1992).
Crystallographic studies of the binding of protonated and unprotonated inhibitors to carbonic anhydrase using hydrogen sulphide and nitrate anions.
  Eur J Biochem, 210, 867-871.
PDB codes: 1can 1cao
1633827 W.Stark, R.A.Pauptit, K.S.Wilson, and J.N.Jansonius (1992).
The structure of neutral protease from Bacillus cereus at 0.2-nm resolution.
  Eur J Biochem, 207, 781-791.
PDB code: 1npc
  2041811 A.Bairoch, and B.Boeckmann (1991).
The SWISS-PROT protein sequence data bank.
  Nucleic Acids Res, 19, 2247-2249.  
  1710977 A.Volbeda, A.Lahm, F.Sakiyama, and D.Suck (1991).
Crystal structure of Penicillium citrinum P1 nuclease at 2.8 A resolution.
  EMBO J, 10, 1607-1618.  
  1949156 M.L.Brader, and M.F.Dunn (1991).
Insulin hexamers: new conformations and applications.
  Trends Biochem Sci, 16, 341-345.  
2111014 J.Y.Liang, and W.N.Lipscomb (1990).
Binding of substrate CO2 to the active site of human carbonic anhydrase II: a molecular dynamics study.
  Proc Natl Acad Sci U S A, 87, 3675-3679.  
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.

 

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