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PDBsum entry 1cny

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protein ligands metals links
Lyase (oxo-acid) PDB id
1cny
Jmol
Contents
Protein chain
256 a.a. *
Ligands
EG3
Metals
_ZN
_HG
Waters ×76
* Residue conservation analysis
PDB id:
1cny
Name: Lyase (oxo-acid)
Title: Secondary interactions significantly removed from the sulfonamide binding pocket of carbonic anhydrase ii influence binding constants
Structure: Carbonic anhydrase ii. Chain: a. Synonym: carbonate dehydratase, hca ii. Ec: 4.2.1.1
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.30Å     R-factor:   0.180    
Authors: P.A.Boriack,D.W.Christianson
Key ref: P.A.Boriack et al. (1995). Secondary interactions significantly removed from the sulfonamide binding pocket of carbonic anhydrase II influence inhibitor binding constants. J Med Chem, 38, 2286-2291. PubMed id: 7608893 DOI: 10.1021/jm00013a004
Date:
21-Jul-95     Release date:   14-Nov-95    
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    
 
 
DOI no: 10.1021/jm00013a004 J Med Chem 38:2286-2291 (1995)
PubMed id: 7608893  
 
 
Secondary interactions significantly removed from the sulfonamide binding pocket of carbonic anhydrase II influence inhibitor binding constants.
P.A.Boriack, D.W.Christianson, J.Kingery-Wood, G.M.Whitesides.
 
  ABSTRACT  
 
A series of competitive inhibitors of carbonic anhydrase II (CAII; EC 4.2.1.1) that consists of oligo(ethylene glycol) units attached to p-benzenesulfonamides with pendant amino acids, H2NSO2C6H4CONHCH2CH2OCH2CH2OCH2CH2NHCOCHRNH3+, have been synthesized and examined using competitive fluorescence assays. Three of the strongest inhibitors, designated EG3NH3+, EG3GlyNH3+, and EG3PheNH3+, have been studied by X-ray crystallographic methods at limiting resolutions of 1.9, 2.0, and 2.3 A, respectively. The sulfonamide-zinc binding modes and the association of the ethylene glycol linkers to the hydrophobic patch of the active site are similar in all three inhibitors. Differences in the values of Kd are therefore not due to differences in zinc coordination or to differences in the modes of enzyme-glycol association but instead appear to arise from interaction of the pendant amino acids with the surface of the protein. These pendant groups are, however, not sufficiently ordered to be visible in electron density maps. Thus, structural variations of inhibitors at locations distant from the primary binding (i.e., the sulfonamide group) site affect the overall binding affinities of inhibitors (e.g., Kd (EG3PheNH3+) = 14 nM as compared with Kd (EG3GluNH3+) = 100 nM).
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19483339 C.Ramalingan, I.S.Lee, and Y.W.Kwak (2009).
Novel furanylarylene arylsulfonylindolesulfonamides: synthesis and their antibacterial evaluation.
  Chem Pharm Bull (Tokyo), 57, 591-596.  
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
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.  
17407288 D.K.Srivastava, K.M.Jude, A.L.Banerjee, M.Haldar, S.Manokaran, J.Kooren, S.Mallik, and D.W.Christianson (2007).
Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II.
  J Am Chem Soc, 129, 5528-5537.
PDB codes: 2nmx 2nn1 2nn7 2nng 2nno 2nns 2nnv
17665409 G.E.Höst, J.Razkin, L.Baltzer, and B.H.Jonsson (2007).
Combined enzyme and substrate design: grafting of a cooperative two-histidine catalytic motif into a protein targeted at the scissile bond in a designed ester substrate.
  Chembiochem, 8, 1570-1576.  
17263415 V.M.Krishnamurthy, V.Semetey, P.J.Bracher, N.Shen, and G.M.Whitesides (2007).
Dependence of effective molarity on linker length for an intramolecular protein-ligand system.
  J Am Chem Soc, 129, 1312-1320.  
16506782 K.M.Jude, A.L.Banerjee, M.K.Haldar, S.Manokaran, B.Roy, S.Mallik, D.K.Srivastava, and D.W.Christianson (2006).
Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors reveal the molecular basis of high affinity.
  J Am Chem Soc, 128, 3011-3018.
PDB codes: 2foq 2fos 2fou 2fov 2foy
16637649 V.M.Krishnamurthy, B.R.Bohall, V.Semetey, and G.M.Whitesides (2006).
The paradoxical thermodynamic basis for the interaction of ethylene glycol, glycine, and sarcosine chains with bovine carbonic anhydrase II: an unexpected manifestation of enthalpy/entropy compensation.
  J Am Chem Soc, 128, 5802-5812.  
16817982 G.M.Whitesides, and V.M.Krishnamurthy (2005).
Designing ligands to bind proteins.
  Q Rev Biophys, 38, 385-395.  
15599912 V.P.Mocharla, B.Colasson, L.V.Lee, S.Röper, K.B.Sharpless, C.H.Wong, and H.C.Kolb (2004).
In situ click chemistry: enzyme-generated inhibitors of carbonic anhydrase II.
  Angew Chem Int Ed Engl, 44, 116-120.  
12500287 C.T.Supuran, A.Scozzafava, and A.Casini (2003).
Carbonic anhydrase inhibitors.
  Med Res Rev, 23, 146-189.  
10785557 C.T.Supuran, F.Briganti, L.Menabuoni, G.Mincione, F.Mincione, and A.Scozzafava (2000).
Carbonic anhydrase inhibitors - part 78(#). Synthesis of water-soluble sulfonamides incorporating beta-alanyl moieties, possessing long lasting-intraocular pressure lowering properties via the topical route.
  Eur J Med Chem, 35, 309-321.  
10425382 C.T.Supuran, A.Scozzafava, L.Menabuoni, F.Mincione, F.Briganti, and G.Mincione (1999).
Carbonic anhydrase inhibitors. Part 71. Synthesis and ocular pharmacology of a new class of water-soluble, topically effective intraocular pressure lowering sulfonamides incorporating picolinoyl moieties.
  Eur J Pharm Sci, 8, 317-328.  
10450978 F.Briganti, A.Scozzafava, and C.T.Supuran (1999).
Novel carbonic anhydrase isozymes I, II and IV activators incorporating sulfonyl-histamino moieties.
  Bioorg Med Chem Lett, 9, 2043-2048.  
10340613 J.G.Harrison, C.Frier, R.Laurant, R.Dennis, K.D.Raney, and S.Balasubramanian (1999).
Inhibition of human telomerase by PNA-cationic peptide conjugates.
  Bioorg Med Chem Lett, 9, 1273-1278.  
10354450 J.Gao, Q.Wu, J.Carbeck, Q.P.Lei, R.D.Smith, and G.M.Whitesides (1999).
Probing the energetics of dissociation of carbonic anhydrase-ligand complexes in the gas phase.
  Biophys J, 76, 3253-3260.  
  9865942 P.A.Boriack-Sjodin, S.Zeitlin, H.H.Chen, L.Crenshaw, S.Gross, A.Dantanarayana, P.Delgado, J.A.May, T.Dean, and D.W.Christianson (1998).
Structural analysis of inhibitor binding to human carbonic anhydrase II.
  Protein Sci, 7, 2483-2489.
PDB codes: 1bn1 1bn3 1bn4 1bnm 1bnn 1bnq 1bnt 1bnu 1bnv 1bnw
9336012 S.Lindskog (1997).
Structure and mechanism of carbonic anhydrase.
  Pharmacol Ther, 74, 1.  
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.