PDBsum entry 1dcb

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protein metals links
Lyase(oxo-acid) PDB id
Jmol PyMol
Protein chain
255 a.a. *
Waters ×93
* Residue conservation analysis
PDB id:
Name: Lyase(oxo-acid)
Title: Structure of an engineered metal binding site in human carbonic anhydrase ii reveals the architecture of a regulatory cysteine switch
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
2.10Å     R-factor:   0.182    
Authors: J.A.Ippolito,D.W.Christianson
Key ref:
J.A.Ippolito and D.W.Christianson (1993). Structure of an engineered His3Cys zinc binding site in human carbonic anhydrase II. Biochemistry, 32, 9901-9905. PubMed id: 8399159 DOI: 10.1021/bi00089a005
10-Mar-93     Release date:   15-Jul-93    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
260 a.a.
255 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.  - 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/bi00089a005 Biochemistry 32:9901-9905 (1993)
PubMed id: 8399159  
Structure of an engineered His3Cys zinc binding site in human carbonic anhydrase II.
J.A.Ippolito, D.W.Christianson.
X-ray crystallographic analysis of the Thr-199-->Cys (T199C) variant of human carbonic anhydrase II reveals the first high-resolution structure of an engineered zinc coordination polyhedron in a metalloenzyme. In the wild-type enzyme, Thr-199 accepts a hydrogen bond from zinc-bound hydroxide; in the variant, the polypeptide backbone is sufficiently plastic to permit Cys-199 to displace hydroxide ion and coordinate to zinc with nearly perfect coordination stereochemistry. Importantly, the resulting His3-Cys-Zn2+ motif binds zinc more tightly than the wild-type enzyme [Kiefer, L. L., Krebs, J. F., Paterno, S. A., & Fierke C. A. (1993) Biochemistry (preceding paper in this issue)]. This novel zinc coordination polyhedron is analogous to that postulated for matrix metalloproteinase zymogens such as prostromelysin, where a cysteine-zinc interaction is responsible for the inactivity of the zymogen. Intriguingly, Cys-199 of T199C CAII is displaced from zinc coordination by soaking crystals in high concentrations of acetazolamide. Hence, residual catalytic activity measured for this variant probably arises from an alternate conformer of Cys-199 which allows the catalytic nucleophile, hydroxide ion, to be activated by zinc coordination.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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
9336012 S.Lindskog (1997).
Structure and mechanism of carbonic anhydrase.
  Pharmacol Ther, 74, 1.  
7761440 J.A.Ippolito, T.T.Baird, S.A.McGee, D.W.Christianson, and C.A.Fierke (1995).
Structure-assisted redesign of a protein-zinc-binding site with femtomolar affinity.
  Proc Natl Acad Sci U S A, 92, 5017-5021.
PDB codes: 1ccs 1cct 1ccu
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