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PDBsum entry 2fnn

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protein ligands metals links
Lyase PDB id
2fnn
Jmol
Contents
Protein chain
258 a.a. *
Ligands
4MZ
Metals
_ZN
Waters ×188
* Residue conservation analysis
PDB id:
2fnn
Name: Lyase
Title: Activation of human carbonic anhydrase ii by exogenous proton donors
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hca ii, ca2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.80Å     R-factor:   0.202     R-free:   0.238
Authors: D.Bhatt,S.Z.Fisher,C.Tu,R.Mckenna,D.N.Silverman
Key ref: D.Bhatt et al. (2007). Location of binding sites in small molecule rescue of human carbonic anhydrase II. Biophys J, 92, 562-570. PubMed id: 17071654
Date:
11-Jan-06     Release date:   28-Nov-06    
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 2 residue positions (black crosses)

 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: 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     5 terms  

 

 
    Added reference    
 
 
Biophys J 92:562-570 (2007)
PubMed id: 17071654  
 
 
Location of binding sites in small molecule rescue of human carbonic anhydrase II.
D.Bhatt, S.Z.Fisher, C.Tu, R.McKenna, D.N.Silverman.
 
  ABSTRACT  
 
Small molecule rescue of mutant forms of human carbonic anhydrase II (HCA II) occurs by participation of exogenous donors/acceptors in the proton transfer pathway between the zinc-bound water and solution. To examine more thoroughly the energetics of this activation, we have constructed a mutant, H64W HCA II, which we have shown is activated by 4-methylimidazole (4-MI) by a mechanism involving the binding of 4-MI to the side chain of Trp-64 approximately 8 A from the zinc. A series of experiments are consistent with the activation of H64W HCA II by the interaction of imidazole and pyridine derivatives as exogenous proton donors with the indole ring of Trp-64; these experiments include pH profiles and H/D solvent isotope effects consistent with proton transfer, observation of approximately fourfold greater activation with the mutant containing Trp-64 compared with Gly-64, and the observation by x-ray crystallography of the binding of 4-MI associated with the indole side chain of Trp-64 in W5A-H64W HCA II. Proton donors bound at the less flexible side chain of Trp-64 in W5A-H64W HCA II do not show activation, but such donors bound at the more flexible Trp-64 of H64W HCA II do show activation, supporting suggestions that conformational mobility of the binding site is associated with more efficient proton transfer. Evaluation using Marcus theory showed that the activation of H64W HCA II by these proton donors was reflected in the work functions w(r) and w(p) rather than in the intrinsic Marcus barrier itself, consistent with the role of solvent reorganization in catalysis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19679199 R.L.Mikulski, and D.N.Silverman (2010).
Proton transfer in catalysis and the role of proton shuttles in carbonic anhydrase.
  Biochim Biophys Acta, 1804, 422-426.  
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.  
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.  
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