PDBsum entry 1fqr

Go to PDB code: 
protein metals links
Lyase PDB id
Jmol PyMol
Protein chain
258 a.a. *
Waters ×80
* Residue conservation analysis
PDB id:
Name: Lyase
Title: X-ray crystal structure of cobalt-bound f93i/f95m/w97v carbonic anhydrase (caii) variant
Structure: Carbonic anhydrase. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
2.00Å     R-factor:   0.216     R-free:   0.275
Authors: J.D.Cox,J.A.Hunt,K.M.Compher,C.A.Fierke,D.W.Christianson
Key ref:
J.D.Cox et al. (2000). Structural influence of hydrophobic core residues on metal binding and specificity in carbonic anhydrase II. Biochemistry, 39, 13687-13694. PubMed id: 11076507 DOI: 10.1021/bi001649j
06-Sep-00     Release date:   17-Jan-01    
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 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Carbonic anhydrase.
[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   22 terms 
  Biochemical function     protein binding     6 terms  


    Added reference    
DOI no: 10.1021/bi001649j Biochemistry 39:13687-13694 (2000)
PubMed id: 11076507  
Structural influence of hydrophobic core residues on metal binding and specificity in carbonic anhydrase II.
J.D.Cox, J.A.Hunt, K.M.Compher, C.A.Fierke, D.W.Christianson.
Aromatic residues in the hydrophobic core of human carbonic anhydrase II (CAII) influence metal ion binding in the active site. Residues F93, F95, and W97 are contained in a beta-strand that also contains two zinc ligands, H94 and H96. The aromatic amino acids contribute to the high zinc affinity and slow zinc dissociation rate constant of CAII [Hunt, J. A., and Fierke, C. A. (1997) J. Biol. Chem. 272, 20364-20372]. Substitution of these aromatic amino acids with smaller side chains enhances Cu(2+) affinity while decreasing Co(2+) and Zn(2+) affinity [Hunt, J. A., Mahiuddin, A., & Fierke, C. A. (1999) Biochemistry 38, 9054-9062]. Here, X-ray crystal structures of zinc-bound F93I/F95M/W97V and F93S/F95L/W97M CAIIs reveal the introduction of new cavities in the hydrophobic core, compensatory movements of surrounding side chains, and the incorporation of buried water molecules; nevertheless, the enzyme maintains tetrahedral zinc coordination geometry. However, a conformational change of direct metal ligand H94 as well as indirect (i.e., "second-shell") ligand Q92 accompanies metal release in both F93I/F95M/W97V and F93S/F95L/W97M CAIIs, thereby eliminating preorientation of the histidine ligands with tetrahedral geometry in the apoenzyme. Only one cobalt-bound variant, F93I/F95M/W97V CAII, maintains tetrahedral metal coordination geometry; F93S/F95L/W97M CAII binds Co(2+) with trigonal bipyramidal coordination geometry due to the addition of azide anion to the metal coordination polyhedron. The copper-bound variants exhibit either square pyramidal or trigonal bipyramidal metal coordination geometry due to the addition of a second solvent molecule to the metal coordination polyhedron. The key finding of this work is that aromatic core residues serve as anchors that help to preorient direct and second-shell ligands to optimize zinc binding geometry and destabilize alternative geometries. These geometrical constraints are likely a main determinant of the enhanced zinc/copper specificity of CAII as compared to small molecule chelators.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19818877 T.K.Hurst, D.Wang, R.B.Thompson, and C.A.Fierke (2010).
Carbonic anhydrase II-based metal ion sensing: Advances and new perspectives.
  Biochim Biophys Acta, 1804, 393-403.  
19583303 B.S.Avvaru, S.A.Busby, M.J.Chalmers, P.R.Griffin, B.Venkatakrishnan, M.Agbandje-McKenna, D.N.Silverman, and R.McKenna (2009).
Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network.
  Biochemistry, 48, 7365-7372.
PDB code: 3gz0
19217874 R.Chiuri, G.Maiorano, A.Rizzello, L.L.del Mercato, R.Cingolani, R.Rinaldi, M.Maffia, and P.P.Pompa (2009).
Exploring local flexibility/rigidity in psychrophilic and mesophilic carbonic anhydrases.
  Biophys J, 96, 1586-1596.  
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.  
17594033 J.Banerjee, M.K.Haldar, S.Manokaran, S.Mallik, and D.K.Srivastava (2007).
New fluorescent probes for carbonic anhydrases.
  Chem Commun (Camb), (), 2723-2725.  
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.