PDBsum entry 3dvb

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protein metals links
Lyase PDB id
Jmol PyMol
Protein chain
258 a.a. *
Waters ×182
* Residue conservation analysis
PDB id:
Name: Lyase
Title: X-ray crystal structure of mutant n62v human carbonic anhydrase ii
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, ca-ii, carbonate dehydratase ii, carbonic anhydrasE C, cac. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 562
1.70Å     R-factor:   0.184     R-free:   0.197
Authors: B.S.Avvaru
Key ref: J.Zheng et al. (2008). Role of hydrophilic residues in proton transfer during catalysis by human carbonic anhydrase II. Biochemistry, 47, 12028-12036. PubMed id: 18942852
18-Jul-08     Release date:   11-Nov-08    
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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 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    
Biochemistry 47:12028-12036 (2008)
PubMed id: 18942852  
Role of hydrophilic residues in proton transfer during catalysis by human carbonic anhydrase II.
J.Zheng, B.S.Avvaru, C.Tu, R.McKenna, D.N.Silverman.
Catalysis by the zinc metalloenzyme human carbonic anhydrase II (HCA II) is limited in maximal velocity by proton transfer between His64 and the zinc-bound solvent molecule. Asn62 extends into the active site cavity of HCA II adjacent to His64 and has been shown to be one of several hydrophilic residues participating in a hydrogen-bonded solvent network within the active site. We compared several site-specific mutants of HCA II with replacements at position 62 (Ala, Val, Leu, Thr, and Asp). The efficiency of catalysis in the hydration of CO 2 for the resulting mutants has been characterized by (18)O exchange, and the structures of the mutants have been determined by X-ray crystallography to 1.5-1.7 A resolution. Each of these mutants maintained the ordered water structure observed by X-ray crystallography in the active site cavity of wild-type HCA II; hence, this water structure was not a variable in comparing with wild type the activities of mutants at residue 62. Crystal structures of wild-type and N62T HCA II showed both an inward and outward orientation of the side chain of His64; however, other mutants in this study showed predominantly inward (N62A, N62V, N62L) or predominantly outward (N62D) orientations of His64. A significant role of Asn62 in HCA II is to permit two conformations of the side chain of His64, the inward and outward, that contributes to maximal efficiency of proton transfer between the active site and solution. The site-specific mutant N62D had a mainly outward orientation of His64, yet the difference in p K a between the proton donor His64 and zinc-bound hydroxide was near zero, as in wild-type HCA II. The rate of proton transfer in catalysis by N62D HCA II was 5% that of wild type, showing that His64 mainly in the outward orientation is associated with inefficient proton transfer compared with His64 in wild type which shows both inward and outward orientations. These results emphasize the roles of the residues of the hydrophilic side of the active site cavity in maintaining efficient catalysis by carbonic anhydrase.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19765680 C.M.Maupin, and G.A.Voth (2010).
Proton transport in carbonic anhydrase: Insights from molecular simulation.
  Biochim Biophys Acta, 1804, 332-341.  
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.  
19634894 C.M.Maupin, J.Zheng, C.Tu, R.McKenna, D.N.Silverman, and G.A.Voth (2009).
Effect of active-site mutation at Asn67 on the proton transfer mechanism of human carbonic anhydrase II.
  Biochemistry, 48, 7996-8005.  
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