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PDBsum entry 4hey

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protein ligands metals links
Lyase PDB id
4hey
Jmol
Contents
Protein chain
257 a.a.
Ligands
4MZ ×9
Metals
_ZN
Waters ×211
PDB id:
4hey
Name: Lyase
Title: Activity enhancers of h64a variant of human carbonic anhydra possess multiple binding sites within and around the enzyme
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonate dehydratase ii, carbonic anhydrasE C, ca carbonic anhydrase ii, ca-ii. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.45Å     R-factor:   0.145     R-free:   0.184
Authors: M.Aggarwal,R.Mckenna
Key ref: M.Aggarwal et al. (2014). Structural insight into activity enhancement and inhibition of H64A carbonic anhydrase II by imidazoles. IUCrJ, 1, 129-135. PubMed id: 25075329 DOI: 10.1107/S2052252514004096
Date:
04-Oct-12     Release date:   23-Oct-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
257 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: 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    
 
 
DOI no: 10.1107/S2052252514004096 IUCrJ 1:129-135 (2014)
PubMed id: 25075329  
 
 
Structural insight into activity enhancement and inhibition of H64A carbonic anhydrase II by imidazoles.
M.Aggarwal, B.Kondeti, C.Tu, C.M.Maupin, D.N.Silverman, R.McKenna.
 
  ABSTRACT  
 
Human carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the hydration and dehydration of CO2 and HCO3 (-), respectively. The reaction follows a ping-pong mechanism, in which the rate-limiting step is the transfer of a proton from the zinc-bound solvent (OH(-)/H2O) in/out of the active site via His64, which is widely believed to be the proton-shuttling residue. The decreased catalytic activity (∼20-fold lower with respect to the wild type) of a variant of CA II in which His64 is replaced with Ala (H64A CA II) can be enhanced by exogenous proton donors/acceptors, usually derivatives of imidazoles and pyridines, to almost the wild-type level. X-ray crystal structures of H64A CA II in complex with four imidazole derivatives (imidazole, 1--methylimidazole, 2--methylimidazole and 4-methylimidazole) have been determined and reveal multiple binding sites. Two of these imidazole binding sites have been identified that mimic the positions of the 'in' and 'out' rotamers of His64 in wild-type CA II, while another directly inhibits catalysis by displacing the zinc-bound solvent. The data presented here not only corroborate the importance of the imidazole side chain of His64 in proton transfer during CA catalysis, but also provide a complete structural understanding of the mechanism by which imidazoles enhance (and inhibit when used at higher concentrations) the activity of H64A CA II.