PDBsum entry 2vva

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protein ligands metals links
Lyase PDB id
Protein chain
258 a.a. *
CO2 ×2
GOL ×2
Waters ×350
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Human carbonic anhydrase in complex with co2
Structure: Carbonic anhydrase 2. Chain: x. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, carbonic anhydrasE C, cac, ca-ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
1.56Å     R-factor:   0.156     R-free:   0.200
Authors: B.Sjoeblom,M.Polentarutti,K.Djinovic-Carugo
Key ref:
B.Sjöblom et al. (2009). Structural study of X-ray induced activation of carbonic anhydrase. Proc Natl Acad Sci U S A, 106, 10609-10613. PubMed id: 19520834 DOI: 10.1073/pnas.0904184106
04-Jun-08     Release date:   14-Jul-09    
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

 Enzyme reactions 
   Enzyme class: E.C.  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
Bound ligand (Het Group name = CO2)
corresponds exactly
+ 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: 10.1073/pnas.0904184106 Proc Natl Acad Sci U S A 106:10609-10613 (2009)
PubMed id: 19520834  
Structural study of X-ray induced activation of carbonic anhydrase.
B.Sjöblom, M.Polentarutti, K.Djinovic-Carugo.
Carbonic anhydrase, a zinc metalloenzyme, catalyzes the reversible hydration of carbon dioxide to bicarbonate. It is involved in processes connected with acid-base homeostasis, respiration, and photosynthesis. More than 100 distinct human carbonic anhydrase II (HCAII) 3D structures have been generated in last 3 decades [Liljas A, et al. (1972) Nat New Biol 235:131-137], but a structure of an HCAII in complex with CO(2) or HCO(3)(-) has remained elusive. Here, we report previously undescribed structures of HCAII:CO(2) and HCAII:HCO(3)(-) complexes, together with a 3D molecular film of the enzymatic reaction observed successively in the same crystal after extended exposure to X-ray. We demonstrate that the unexpected enzyme activation was caused in an X-ray dose-dependent manner. Although X-ray damage to macromolecular samples has long been recognized [Ravelli RB, Garman EF (2006) Curr Opin Struct Biol 16:624-629], the detailed structural analysis reports on X-ray-driven reactions have been very rare in literature to date. Here, we report on enzyme activation and the associated chemical reaction in a crystal at 100 K. We propose mechanisms based on water photoradiolysis and/or electron radiolysis as the main cause of enzyme activation.
  Selected figure(s)  
Figure 2.
Stereoview of HCAII in complex with carbon dioxide and bicarbonate. Distances listed below are indicated in the figures by dashed lines. (A) The 1σ level 2|F[o]| − |F[c]| electron density map and corresponding model for the CO[2]-loaded HCAII active site at 1.56-Å resolution. The carbon dioxide O2 atom is at a hydrogen-bonding distance of 3.4 Å from the main chain nitrogen of Thr-199, Wat-338 (3.1 Å), and Wat-263 (3.1 Å). The CO[2] molecule also makes van der Waals contacts with all residues lining the hydrophobic pocket (Val-121, Val-143, Leu-198, and Trp-209) and the zinc ligands His-94 and His-119. (B) The 1σ level 2|Fo| – |Fc| electron density maps and the corresponding model for the complex of HCAII and bicarbonate at 1.66-Å resolution. The O3 oxygen of bicarbonate is bound to the zinc ion at 2.0 Å and is within hydrogen-bonding distance of Wat-318 (2.4 Å), Thr-199 OG1 (2.6 Å), and Wat-338 (2.9 Å). The bicarbonate O2 atom is within hydrogen-bonding distance of Wat-338 (2.7 Å) and Thr-199 N (3.1 Å). The O1 atom of bicarbonate is 2.9 Å away from the zinc ion. The HCO[3]^− has van der Waals contacts with the same residues as CO[2] (see A).
Figure 3.
Stereoview of the overlay of the resting enzyme with the substrate and product. Superposition of active sites of resting enzyme (red), enzyme with CO[2] substrate (green), and enzyme with bound HCO[3]^− (yellow). Arrows indicate potential pathways of the water molecules from the entrance of the active-site channel toward the catalytic site.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21525638 E.F.Garman, and M.Weik (2011).
Macromolecular crystallography radiation damage research: what's new?
  J Synchrotron Radiat, 18, 313-317.  
20000378 B.S.Avvaru, C.U.Kim, K.H.Sippel, S.M.Gruner, M.Agbandje-McKenna, D.N.Silverman, and R.McKenna (2010).
A short, strong hydrogen bond in the active site of human carbonic anhydrase II.
  Biochemistry, 49, 249-251.
PDB code: 3ks3
20382986 E.F.Garman (2010).
Radiation damage in macromolecular crystallography: what is it and why should we care?
  Acta Crystallogr D Biol Crystallogr, 66, 339-351.  
19679198 J.F.Domsic, and R.McKenna (2010).
Sequestration of carbon dioxide by the hydrophobic pocket of the carbonic anhydrases.
  Biochim Biophys Acta, 1804, 326-331.  
21070940 P.Carpentier, A.Royant, M.Weik, and D.Bourgeois (2010).
Raman-assisted crystallography suggests a mechanism of X-ray-induced disulfide radical formation and reparation.
  Structure, 18, 1410-1419.
PDB codes: 2xbr 2xbs
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.  
20025241 S.Z.Fisher, A.Y.Kovalevsky, J.F.Domsic, M.Mustyakimov, R.McKenna, D.N.Silverman, and P.A.Langan (2010).
Neutron structure of human carbonic anhydrase II: implications for proton transfer.
  Biochemistry, 49, 415-421.
PDB code: 3kkx
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