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PDBsum entry 1ca2

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protein metals links
Lyase(oxo-acid) PDB id
1ca2
Jmol
Contents
Protein chain
256 a.a. *
Metals
_ZN
Waters ×167
* Residue conservation analysis
PDB id:
1ca2
Name: Lyase(oxo-acid)
Title: Refined structure of human carbonic anhydrase ii at 2.0 angstroms resolution
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.00Å     R-factor:   0.173    
Authors: A.E.Eriksson,T.A.Jones,A.Liljas
Key ref: A.E.Eriksson et al. (1988). Refined structure of human carbonic anhydrase II at 2.0 A resolution. Proteins, 4, 274-282. PubMed id: 3151019
Date:
06-Feb-89     Release date:   15-Jan-90    
Supersedes: 1cac
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
256 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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   21 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
Proteins 4:274-282 (1988)
PubMed id: 3151019  
 
 
Refined structure of human carbonic anhydrase II at 2.0 A resolution.
A.E.Eriksson, T.A.Jones, A.Liljas.
 
  ABSTRACT  
 
The structure of human erythrocytic carbonic anhydrase II has been refined by constrained and restrained structure-factor least-squares refinement at 2.0 A resolution. The conventional crystallographic R value is 17.3%. Of 167 solvent molecules associated with the protein, four are buried and stabilize secondary structure elements. The zinc ion is ligated to three histidyl residues and one water molecule in a nearly tetrahedral geometry. In addition to the zinc-bound water, seven more water molecules are identified in the active site. Assuming that Glu-106 is deprotonated at pH 8.5, some of the hydrogen bond donor-acceptor relations in the active site can be assigned and are described here in detail. The O gamma 1 atom of Thr-199 donates its proton to the O epsilon 1 atom of Glu-106 and can function as a hydrogen bond acceptor only in additional hydrogen bonds.
 

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
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
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
20686683 R.Potestio, C.Micheletti, and H.Orland (2010).
Knotted vs. unknotted proteins: evidence of knot-promoting loops.
  PLoS Comput Biol, 6, e1000864.  
20505865 V.Alterio, S.M.Monti, E.Truppo, C.Pedone, C.T.Supuran, and G.De Simone (2010).
The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex.
  Org Biomol Chem, 8, 3528-3533.
PDB code: 3lxe
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.  
19588465 D.Aili, R.Selegård, L.Baltzer, K.Enander, and B.Liedberg (2009).
Colorimetric protein sensing by controlled assembly of gold nanoparticles functionalized with synthetic receptors.
  Small, 5, 2445-2452.  
19691272 M.N.Weaver, Y.Yang, and K.M.Merz (2009).
Assessment of the CCSD and CCSD(T) coupled-cluster methods in calculating heats of formation for Zn complexes.
  J Phys Chem A, 113, 10081-10088.  
19805286 V.Alterio, M.Hilvo, A.Di Fiore, C.T.Supuran, P.Pan, S.Parkkila, A.Scaloni, J.Pastorek, S.Pastorekova, C.Pedone, A.Scozzafava, S.M.Monti, and G.De Simone (2009).
Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX.
  Proc Natl Acad Sci U S A, 106, 16233-16238.
PDB code: 3iai
19085026 W.A.Eger, B.O.Jahn, and E.Anders (2009).
The zinc complex catalyzed hydration of alkyl isothiocyanates.
  J Mol Model, 15, 433-446.  
19278252 Y.Lin, Z.Cao, and Y.Mo (2009).
Functional role of Asp160 and the deprotonation mechanism of ammonium in the Escherichia coli ammonia channel protein AmtB.
  J Phys Chem B, 113, 4922-4929.  
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.  
18600270 C.Temperini, A.Cecchi, A.Scozzafava, and C.T.Supuran (2008).
Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited--old leads for new applications?
  Org Biomol Chem, 6, 2499-2506.  
18161740 K.D'Ambrosio, B.Masereel, A.Thiry, A.Scozzafava, C.T.Supuran, and G.De Simone (2008).
Carbonic anhydrase inhibitors: binding of indanesulfonamides to the human isoform II.
  ChemMedChem, 3, 473-477.
PDB codes: 2qo8 2qoa
18359862 M.C.Bauer, H.Nilsson, E.Thulin, B.Frohm, J.Malm, and S.Linse (2008).
Zn2+ binding to human calbindin D(28k) and the role of histidine residues.
  Protein Sci, 17, 760-767.  
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.  
18060825 Y.Jiang, J.T.Su, J.Zhang, X.Wei, Y.B.Yan, and H.M.Zhou (2008).
Reshaping the folding energy landscape of human carbonic anhydrase II by a single point genetic mutation Pro237His.
  Int J Biochem Cell Biol, 40, 776-788.  
17552801 A.Jezierska, J.J.Panek, A.Koll, and J.Mavri (2007).
Car-Parrinello simulation of an O-H stretching envelope and potential of mean force of an intramolecular hydrogen bonded system: application to a Mannich base in solid state and in vacuum.
  J Chem Phys, 126, 205101.  
17319695 C.M.Maupin, and G.A.Voth (2007).
Preferred orientations of His64 in human carbonic anhydrase II.
  Biochemistry, 46, 2938-2947.  
17573429 S.Marino, K.Hayakawa, K.Hatada, M.Benfatto, A.Rizzello, M.Maffia, and L.Bubacco (2007).
Structural features that govern enzymatic activity in carbonic anhydrase from a low-temperature adapted fish, Chionodraco hamatus.
  Biophys J, 93, 2781-2790.  
17165785 D.Riccardi, P.König, X.Prat-Resina, H.Yu, M.Elstner, T.Frauenheim, and Q.Cui (2006).
"Proton holes" in long-range proton transfer reactions in solution and enzymes: A theoretical analysis.
  J Am Chem Soc, 128, 16302-16311.  
16416502 K.Okrasa, and R.J.Kazlauskas (2006).
Manganese-substituted carbonic anhydrase as a new peroxidase.
  Chemistry, 12, 1587-1596.  
16405327 P.H.König, N.Ghosh, M.Hoffmann, M.Elstner, E.Tajkhorshid, T.Frauenheim, and Q.Cui (2006).
Toward theoretical analysis of long-range proton transfer kinetics in biomolecular pumps.
  J Phys Chem A, 110, 548-563.  
16156801 E.Paci, L.H.Greene, R.M.Jones, and L.J.Smith (2005).
Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach.
  FEBS J, 272, 4826-4838.  
15929995 R.Afrin, M.T.Alam, and A.Ikai (2005).
Pretransition and progressive softening of bovine carbonic anhydrase II as probed by single molecule atomic force microscopy.
  Protein Sci, 14, 1447-1457.  
16298304 T.Andersson, M.Lundquist, G.T.Dolphin, K.Enander, B.H.Jonsson, J.W.Nilsson, and L.Baltzer (2005).
The binding of human carbonic anhydrase II by functionalized folded polypeptide receptors.
  Chem Biol, 12, 1245-1252.  
15039588 R.Saito, T.Sato, A.Ikai, and N.Tanaka (2004).
Structure of bovine carbonic anhydrase II at 1.95 A resolution.
  Acta Crystallogr D Biol Crystallogr, 60, 792-795.
PDB code: 1v9e
12171926 C.Tu, M.Qian, H.An, N.R.Wadhwa, D.Duda, C.Yoshioka, Y.Pathak, R.McKenna, P.J.Laipis, and D.N.Silverman (2002).
Kinetic analysis of multiple proton shuttles in the active site of human carbonic anhydrase.
  J Biol Chem, 277, 38870-38876.
PDB code: 1lzv
11976500 D.M.Duda, C.Yoshioka, L.Govindasamy, H.An, C.Tu, D.N.Silverman, and R.McKenna (2002).
Crystallization and preliminary X-ray analysis of human carbonic anhydrase III.
  Acta Crystallogr D Biol Crystallogr, 58, 849-852.  
12009884 M.Ferraroni, S.Tilli, F.Briganti, W.R.Chegwidden, C.T.Supuran, K.E.Wiebauer, R.E.Tashian, and A.Scozzafava (2002).
Crystal structure of a zinc-activated variant of human carbonic anhydrase I, CA I Michigan 1: evidence for a second zinc binding site involving arginine coordination.
  Biochemistry, 41, 6237-6244.
PDB codes: 1j9w 1jv0
12056894 S.Huang, B.Sjöblom, A.E.Sauer-Eriksson, and B.H.Jonsson (2002).
Organization of an efficient carbonic anhydrase: implications for the mechanism based on structure-function studies of a T199P/C206S mutant.
  Biochemistry, 41, 7628-7635.
PDB codes: 1lg5 1lg6 1lgd
11468394 M.J.Ellis, F.E.Dodd, R.W.Strange, M.Prudêncio, G.Sawers, R.R.Eady, and S.S.Hasnain (2001).
X-ray structure of a blue copper nitrite reductase at high pH and in copper-free form at 1.9 A resolution.
  Acta Crystallogr D Biol Crystallogr, 57, 1110-1118.
PDB codes: 1hau 1haw
11828444 M.Mauksch, M.Bräuer, J.Weston, and E.Anders (2001).
New insights into the mechanistic details of the carbonic anhydrase cycle as derived from the model system [(NH(3))(3)Zn(OH)](+)/CO(2): how does the H(2)O/HCO(3)(-) replacement step occur?
  Chembiochem, 2, 190-198.  
11371461 M.Persson, J.R.Harbridge, P.Hammarström, R.Mitri, L.G.Mårtensson, U.Carlsson, G.R.Eaton, and S.S.Eaton (2001).
Comparison of electron paramagnetic resonance methods to determine distances between spin labels on human carbonic anhydrase II.
  Biophys J, 80, 2886-2897.  
11371460 P.Hammarström, R.Owenius, L.G.Mårtensson, U.Carlsson, and M.Lindgren (2001).
High-resolution probing of local conformational changes in proteins by the use of multiple labeling: unfolding and self-assembly of human carbonic anhydrase II monitored by spin, fluorescent, and chemical reactivity probes.
  Biophys J, 80, 2867-2885.  
11121027 B.Ulmasov, A.Waheed, G.N.Shah, J.H.Grubb, W.S.Sly, C.Tu, and D.N.Silverman (2000).
Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers.
  Proc Natl Acad Sci U S A, 97, 14212-14217.  
10978542 K.S.Smith, and J.G.Ferry (2000).
Prokaryotic carbonic anhydrases.
  FEMS Microbiol Rev, 24, 335-366.  
  10794421 R.E.Burton, J.A.Hunt, C.A.Fierke, and T.G.Oas (2000).
Novel disulfide engineering in human carbonic anhydrase II using the PAIRWISE side-chain geometry database.
  Protein Sci, 9, 776-785.  
10551854 P.Hammarström, M.Persson, P.O.Freskgârd, L.G.Mârtensson, D.Andersson, B.H.Jonsson, and U.Carlsson (1999).
Structural mapping of an aggregation nucleation site in a molten globule intermediate.
  J Biol Chem, 274, 32897-32903.  
9635771 C.Tu, M.Qian, J.N.Earnhardt, P.J.Laipis, and D.N.Silverman (1998).
Properties of intramolecular proton transfer in carbonic anhydrase III.
  Biophys J, 74, 3182-3189.  
9852049 D.L.Daugherty, D.Rozema, P.E.Hanson, and S.H.Gellman (1998).
Artificial chaperone-assisted refolding of citrate synthase.
  J Biol Chem, 273, 33961-33971.  
  10082367 I.L.Alberts, K.Nadassy, and S.J.Wodak (1998).
Analysis of zinc binding sites in protein crystal structures.
  Protein Sci, 7, 1700-1716.  
9485356 J.Gallagher, O.Zelenko, A.D.Walts, and D.S.Sigman (1998).
Protease activity of 1,10-phenanthroline-copper(I). Targeted scission of the catalytic site of carbonic anhydrase.
  Biochemistry, 37, 2096-2104.  
8995407 M.L.Brader, N.C.Kaarsholm, S.E.Harnung, and M.F.Dunn (1997).
Ligand perturbation effects on a pseudotetrahedral Co(II)(His)3-ligand site. A magnetic circular dichroism study of the Co(II)-substituted insulin hexamer.
  J Biol Chem, 272, 1088-1094.  
9336012 S.Lindskog (1997).
Structure and mechanism of carbonic anhydrase.
  Pharmacol Ther, 74, 1.  
8807898 A.M.Schmidt, H.N.Müller, and A.Skerra (1996).
A Zn(II)-binding site engineered into retinol-binding protein exhibits metal-ion specificity and allows highly efficient affinity purification with a newly designed metal ligand.
  Chem Biol, 3, 645-653.  
  8976556 K.Borén, P.O.Freskgård, and U.Carlsson (1996).
A comparative CD study of carbonic anhydrase isoenzymes with different number of tryptophans: impact on calculation of secondary structure content.
  Protein Sci, 5, 2479-2484.  
7669898 M.Lindgren, M.Svensson, P.O.Freskgård, U.Carlsson, P.Jonasson, L.G.Mårtensson, and B.H.Jonsson (1995).
Characterization of a folding intermediate of human carbonic anhydrase II: probing local mobility by electron paramagnetic resonance.
  Biophys J, 69, 202-213.  
7696308 M.Persson, G.Aronsson, N.Bergenhem, P.O.Freskgård, B.H.Jonsson, B.P.Surin, M.D.Spangfort, and U.Carlsson (1995).
GroEL/ES-mediated refolding of human carbonic anhydrase II: role of N-terminal helices as recognition motifs for GroEL.
  Biochim Biophys Acta, 1247, 195-200.  
7479916 P.A.Boriack-Sjodin, R.W.Heck, P.J.Laipis, D.N.Silverman, and D.W.Christianson (1995).
Structure determination of murine mitochondrial carbonic anhydrase V at 2.45-A resolution: implications for catalytic proton transfer and inhibitor design.
  Proc Natl Acad Sci U S A, 92, 10949-10953.
PDB codes: 1dmx 1dmy
8539245 R.H.Stote, and M.Karplus (1995).
Zinc binding in proteins and solution: a simple but accurate nonbonded representation.
  Proteins, 23, 12-31.  
7796265 R.W.Strange, F.E.Dodd, Z.H.Abraham, J.G.Grossmann, T.Brüser, R.R.Eady, B.E.Smith, and S.S.Hasnain (1995).
The substrate-binding site in Cu nitrite reductase and its similarity to Zn carbonic anhydrase.
  Nat Struct Biol, 2, 287-292.  
8306976 A.Liljas, K.Håkansson, B.H.Jonsson, and Y.Xue (1994).
Inhibition and catalysis of carbonic anhydrase. Recent crystallographic analyses.
  Eur J Biochem, 219, 1.  
  8003972 C.L.Borders, J.A.Broadwater, P.A.Bekeny, J.E.Salmon, A.S.Lee, A.M.Eldridge, and V.B.Pett (1994).
A structural role for arginine in proteins: multiple hydrogen bonds to backbone carbonyl oxygens.
  Protein Sci, 3, 541-548.  
8203021 D.C.Richardson, and J.S.Richardson (1994).
Kinemages--simple macromolecular graphics for interactive teaching and publication.
  Trends Biochem Sci, 19, 135-138.  
7925414 I.M.Johansson, and C.Forsman (1994).
Solvent hydrogen isotope effects and anion inhibition of CO2 hydration catalysed by carbonic anhydrase from Pisum sativum.
  Eur J Biochem, 224, 901-907.  
8497481 A.E.Eriksson, and A.Liljas (1993).
Refined structure of bovine carbonic anhydrase III at 2.0 A resolution.
  Proteins, 16, 29-42.  
  8382771 G.Barnea, O.Silvennoinen, B.Shaanan, A.M.Honegger, P.D.Canoll, P.D'Eustachio, B.Morse, J.B.Levy, S.Laforgia, and K.Huebner (1993).
Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases.
  Mol Cell Biol, 13, 1497-1506.  
8269932 I.M.Johansson, and C.Forsman (1993).
Kinetic studies of pea carbonic anhydrase.
  Eur J Biochem, 218, 439-446.  
8441752 M.Lindahl, L.A.Svensson, and A.Liljas (1993).
Metal poison inhibition of carbonic anhydrase.
  Proteins, 15, 177-182.  
8400138 N.J.Provart, N.Majeau, and J.R.Coleman (1993).
Characterization of pea chloroplastic carbonic anhydrase. Expression in Escherichia coli and site-directed mutagenesis.
  Plant Mol Biol, 22, 937-943.  
8473916 S.H.Rotstein, and M.A.Murcko (1993).
GenStar: a method for de novo drug design.
  J Comput Aided Mol Des, 7, 23-43.  
8477723 S.K.Nair, and D.W.Christianson (1993).
Crystallographic studies of azide binding to human carbonic anhydrase II.
  Eur J Biochem, 213, 507-515.  
7901850 Y.Xue, A.Liljas, B.H.Jonsson, and S.Lindskog (1993).
Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II.
  Proteins, 17, 93.
PDB codes: 1cai 1caj 1cak 1cal 1cam
8451242 Y.Xue, J.Vidgren, L.A.Svensson, A.Liljas, B.H.Jonsson, and S.Lindskog (1993).
Crystallographic analysis of Thr-200-->His human carbonic anhydrase II and its complex with the substrate, HCO3-.
  Proteins, 15, 80-87.
PDB code: 1bic
8265567 Z.Peng, K.M.Merz, and L.Banci (1993).
Binding of cyanide, cyanate, and thiocyanate to human carbonic anhydrase II.
  Proteins, 17, 203-216.  
  1598233 A.Bairoch, and B.Boeckmann (1992).
The SWISS-PROT protein sequence data bank.
  Nucleic Acids Res, 20, 2019-2022.  
  1304880 D.C.Richardson, and J.S.Richardson (1992).
The kinemage: a tool for scientific communication.
  Protein Sci, 1, 3-9.  
  1304887 E.Meyer (1992).
Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications.
  Protein Sci, 1, 1543-1562.  
1420895 L.Banci, L.B.Dugad, G.N.La Mar, K.A.Keating, C.Luchinat, and R.Pierattelli (1992).
1H nuclear magnetic resonance investigation of cobalt(II) substituted carbonic anhydrase.
  Biophys J, 63, 530-543.  
1323835 N.X.Krueger, and H.Saito (1992).
A human transmembrane protein-tyrosine-phosphatase, PTP zeta, is expressed in brain and has an N-terminal receptor domain homologous to carbonic anhydrases.
  Proc Natl Acad Sci U S A, 89, 7417-7421.  
1336460 S.Mangani, and K.Håkansson (1992).
Crystallographic studies of the binding of protonated and unprotonated inhibitors to carbonic anhydrase using hydrogen sulphide and nitrate anions.
  Eur J Biochem, 210, 867-871.
PDB codes: 1can 1cao
  2041811 A.Bairoch, and B.Boeckmann (1991).
The SWISS-PROT protein sequence data bank.
  Nucleic Acids Res, 19, 2247-2249.  
  1949156 M.L.Brader, and M.F.Dunn (1991).
Insulin hexamers: new conformations and applications.
  Trends Biochem Sci, 16, 341-345.  
1909971 P.O.Freskgård, U.Carlsson, L.G.Mårtensson, and B.H.Jonsson (1991).
Folding around the C-terminus of human carbonic anhydrase II. Kinetic characterization by use of a chemically reactive SH-group introduced by protein engineering.
  FEBS Lett, 289, 117-122.  
3151020 A.E.Eriksson, P.M.Kylsten, T.A.Jones, and A.Liljas (1988).
Crystallographic studies of inhibitor binding sites in human carbonic anhydrase II: a pentacoordinated binding of the SCN- ion to the zinc at high pH.
  Proteins, 4, 283-293.
PDB codes: 2ca2 3ca2
3151019 A.E.Eriksson, T.A.Jones, and A.Liljas (1988).
Refined structure of human carbonic anhydrase II at 2.0 A resolution.
  Proteins, 4, 274-282.
PDB codes: 1ca2 4cac 5cac
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.