spacer
spacer

PDBsum entry 2ili

Go to PDB code: 
protein metals links
Lyase PDB id
2ili
Jmol PyMol
Contents
Protein chain
258 a.a. *
Metals
_ZN
Waters ×311
* Residue conservation analysis
PDB id:
2ili
Name: Lyase
Title: Refine atomic structure of human carbonic anhydrase ii
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
1.05Å     R-factor:   0.120     R-free:   0.151
Authors: S.Z.Fisher
Key ref: S.Z.Fisher et al. (2007). Atomic crystal and molecular dynamics simulation structures of human carbonic anhydrase II: insights into the proton transfer mechanism. Biochemistry, 46, 2930-2937. PubMed id: 17319692
Date:
02-Oct-06     Release date:   05-Jun-07    
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

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.1  - Carbonic anhydrase.
[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     6 terms  

 

 
    Added reference    
 
 
Biochemistry 46:2930-2937 (2007)
PubMed id: 17319692  
 
 
Atomic crystal and molecular dynamics simulation structures of human carbonic anhydrase II: insights into the proton transfer mechanism.
S.Z.Fisher, C.M.Maupin, M.Budayova-Spano, L.Govindasamy, C.Tu, M.Agbandje-McKenna, D.N.Silverman, G.A.Voth, R.McKenna.
 
  ABSTRACT  
 
Human carbonic anhydrase II (HCA II) is a zinc-metalloenzyme that catalyzes the reversible interconversion of CO2 and HCO3-. The rate-limiting step of this catalysis is the transfer of a proton between the Zn-bound solvent molecule and residue His64. In order to fully characterize the active site structural features implicated in the proton transfer mechanism, the refined X-ray crystal structure of uncomplexed wild type HCA II to 1.05 A resolution with an Rcryst value of 12.0% and an Rfree value of 15.1% has been elucidated. This structure provides strong clues as to the pathway of the intramolecular proton transfer between the Zn-bound solvent and His64. The structure emphasizes the role of the solvent network, the unique positioning of solvent molecule W2, and the significance of the dual conformation of His64 in the active site. The structure is compared with molecular dynamics (MD) simulation calculations of the Zn-bound hydroxyl/His64+ (charged) and the Zn-bound water/His64 (uncharged) HCA II states. A comparison of the crystallographic anisotropic atomic thermal parameters and MD simulation root-mean-square fluctuation values show excellent agreement in the atomic motion observed between the two methods. It is also interesting that the observed active site solvent positions in the crystal structure are also the most probable positions of the solvent during the MD simulations. On the basis of the comparative study of the MD simulation results, the HCA II crystal structure observed is most likely in the Zn-bound water/His64 state. This conclusion is based on the following observations: His64 is mainly (80%) orientated in an inward conformation; electron density omit maps infer that His64 is not charged in an either inward or outward conformation; and the Zn-bound solvent is most likely a water molecule.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21515057 F.Carta, V.Garaj, A.Maresca, J.Wagner, B.S.Avvaru, A.H.Robbins, A.Scozzafava, R.McKenna, and C.T.Supuran (2011).
Sulfonamides incorporating 1,3,5-triazine moieties selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII and XIV over cytosolic isoforms I and II: Solution and X-ray crystallographic studies.
  Bioorg Med Chem, 19, 3105-3119.
PDB codes: 3mmf 3mna
21282642 H.M.Becker, M.Klier, C.Schüler, R.McKenna, and J.W.Deitmer (2011).
Intramolecular proton shuttle supports not only catalytic but also noncatalytic function of carbonic anhydrase II.
  Proc Natl Acad Sci U S A, 108, 3071-3076.  
20445238 A.H.Robbins, J.F.Domsic, M.Agbandje-McKenna, and R.McKenna (2010).
Structure of a monoclinic polymorph of human carbonic anhydrase II with a doubled a axis.
  Acta Crystallogr D Biol Crystallogr, 66, 628-634.
PDB code: 3ks1
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
20445237 C.A.Behnke, I.Le Trong, J.W.Godden, E.A.Merritt, D.C.Teller, J.Bajorath, and R.E.Stenkamp (2010).
Atomic resolution studies of carbonic anhydrase II.
  Acta Crystallogr D Biol Crystallogr, 66, 616-627.
PDB codes: 1lug 3k34
19765680 C.M.Maupin, and G.A.Voth (2010).
Proton transport in carbonic anhydrase: Insights from molecular simulation.
  Biochim Biophys Acta, 1804, 332-341.  
20922253 F.Pacchiano, M.Aggarwal, B.S.Avvaru, A.H.Robbins, A.Scozzafava, R.McKenna, and C.T.Supuran (2010).
Selective hydrophobic pocket binding observed within the carbonic anhydrase II active site accommodate different 4-substituted-ureido-benzenesulfonamides and correlate to inhibitor potency.
  Chem Commun (Camb), 46, 8371-8373.
PDB codes: 3mzc 3n0n 3n2p 3n3j 3n4b
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.  
20640250 J.Murillo, J.David, and A.Restrepo (2010).
Insights into the structure and stability of the carbonic acid dimer.
  Phys Chem Chem Phys, 12, 10963-10970.  
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
19583303 B.S.Avvaru, S.A.Busby, M.J.Chalmers, P.R.Griffin, B.Venkatakrishnan, M.Agbandje-McKenna, D.N.Silverman, and R.McKenna (2009).
Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network.
  Biochemistry, 48, 7365-7372.
PDB code: 3gz0
19170619 C.Genis, K.H.Sippel, N.Case, W.Cao, B.S.Avvaru, L.J.Tartaglia, L.Govindasamy, C.Tu, M.Agbandje-McKenna, D.N.Silverman, C.J.Rosser, and R.McKenna (2009).
Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties.
  Biochemistry, 48, 1322-1331.
PDB codes: 3d8w 3d9z 3daz 3dbu 3dc3 3dc9 3dcc 3dcs 3dcw 3dd0
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.  
  19851004 K.H.Sippel, A.H.Robbins, J.Domsic, C.Genis, M.Agbandje-McKenna, and R.McKenna (2009).
High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 992-995.
PDB code: 3hs4
  19407386 S.Z.Fisher, A.Y.Kovalevsky, J.F.Domsic, M.Mustyakimov, D.N.Silverman, R.McKenna, and P.Langan (2009).
Preliminary joint neutron and X-ray crystallographic study of human carbonic anhydrase II.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 495-498.  
18671353 C.M.Maupin, M.G.Saunders, I.F.Thorpe, R.McKenna, D.N.Silverman, and G.A.Voth (2008).
Origins of enhanced proton transport in the Y7F mutant of human carbonic anhydrase II.
  J Am Chem Soc, 130, 11399-11408.  
19036170 F.Bootorabi, J.Jänis, J.Valjakka, S.Isoniemi, P.Vainiotalo, D.Vullo, C.T.Supuran, A.Waheed, W.S.Sly, O.Niemelä, and S.Parkkila (2008).
Modification of carbonic anhydrase II with acetaldehyde, the first metabolite of ethanol, leads to decreased enzyme activity.
  BMC Biochem, 9, 32.  
18768466 J.F.Domsic, B.S.Avvaru, C.U.Kim, S.M.Gruner, M.Agbandje-McKenna, D.N.Silverman, and R.McKenna (2008).
Entrapment of Carbon Dioxide in the Active Site of Carbonic Anhydrase II.
  J Biol Chem, 283, 30766-30771.
PDB codes: 3d92 3d93
18589895 J.Seravalli, and S.W.Ragsdale (2008).
13C NMR characterization of an exchange reaction between CO and CO2 catalyzed by carbon monoxide dehydrogenase.
  Biochemistry, 47, 6770-6781.  
18942852 J.Zheng, B.S.Avvaru, C.Tu, R.McKenna, and D.N.Silverman (2008).
Role of hydrophilic residues in proton transfer during catalysis by human carbonic anhydrase II.
  Biochemistry, 47, 12028-12036.
PDB codes: 3dv7 3dvb 3dvc 3dvd
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.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

spacer

spacer