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PDBsum entry 1avn

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protein ligands metals links
Lyase PDB id
1avn
Jmol
Contents
Protein chain
257 a.a. *
Ligands
AZI
HSM
Metals
_ZN
_HG
Waters ×155
* Residue conservation analysis
PDB id:
1avn
Name: Lyase
Title: Human carbonic anhydrase ii complexed with the histamine activator
Structure: Carbonic anhydrase ii. Chain: a. Synonym: hca ii. Engineered: yes. Other_details: complex with histamine
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Cell: erythrocytes. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.00Å     R-factor:   0.154    
Authors: F.Briganti,S.Mangani,P.Orioli,A.Scozzafava,G.Vernaglione, C.T.Supuran
Key ref:
F.Briganti et al. (1997). Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine. Biochemistry, 36, 10384-10392. PubMed id: 9265618 DOI: 10.1021/bi970760v
Date:
17-Sep-97     Release date:   24-Dec-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
257 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/bi970760v Biochemistry 36:10384-10392 (1997)
PubMed id: 9265618  
 
 
Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine.
F.Briganti, S.Mangani, P.Orioli, A.Scozzafava, G.Vernaglione, C.T.Supuran.
 
  ABSTRACT  
 
The interaction of native and Co(II)-substituted isozymes I and II of carbonic anhydrase (CA) with histamine, a well-known activator, was investigated kinetically, spectroscopically, and X-ray crystallographically. This activator is of the noncompetitive type with 4-nitrophenyl acetate and CO2 as substrates for both HCA I and HCA II. The electronic spectrum of the adduct of Co(II)-HCA II with histamine is similar to the spectrum of the Co(II)-HCA II-phenol adduct, being only slightly different from that of the uncomplexed enzyme. This is the first spectroscopic evidence that the activator molecule binds within the active site, but not directly to the metal ion. X-ray crystallographic data for the adduct of HCA II with histamine showed that the activator molecule is bound at the entrance of the active site cavity in a position where it may actively participate in shuttling protons between the active site and the bulk solvent. The role of the activators and the reported X-ray crystal structure of the HCA II-histamine adduct has prompted us to reexamine the X-ray structures of the different CA isozymes in order to find a structural basis accounting for their large differences in catalytic rate. A tentative explanation is proposed on the basis of possible pathways of proton transfer, which constitute the rate-limiting step in the catalytic reaction.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21369613 K.Dave, A.Scozzafava, D.Vullo, C.T.Supuran, and M.A.Ilies (2011).
Pyridinium derivatives of histamine are potent activators of cytosolic carbonic anhydrase isoforms I, II and VII.
  Org Biomol Chem, 9, 2790-2800.  
21036610 K.Dave, M.A.Ilies, A.Scozzafava, C.Temperini, D.Vullo, and C.T.Supuran (2011).
An inhibitor-like binding mode of a carbonic anhydrase activator within the active site of isoform II.
  Bioorg Med Chem Lett, 21, 2764-2768.  
20931644 A.Casini, C.Temperini, C.Gabbiani, C.T.Supuran, and L.Messori (2010).
The x-ray structure of the adduct between NAMI-A and carbonic anhydrase provides insights into the reactivity of this metallodrug with proteins.
  ChemMedChem, 5, 1989-1994.
PDB code: 3m1j
20118557 A.Sugimoto, H.Ikeda, H.Tsukamoto, K.Kihira, M.Ishioka, J.Hirose, T.Hata, H.Fujioka, and Y.Ono (2010).
Timolol activates the enzyme activities of human carbonic anhydrase I and II.
  Biol Pharm Bull, 33, 301-306.  
20629007 J.Schulze Wischeler, A.Innocenti, D.Vullo, A.Agrawal, S.M.Cohen, A.Heine, C.T.Supuran, and G.Klebe (2010).
Bidentate Zinc chelators for alpha-carbonic anhydrases that produce a trigonal bipyramidal coordination geometry.
  ChemMedChem, 5, 1609-1615.
PDB code: 3m1k
19360879 S.S.Picaud, J.R.Muniz, A.Kramm, E.S.Pilka, G.Kochan, U.Oppermann, and W.W.Yue (2009).
Crystal structure of human carbonic anhydrase-related protein VIII reveals the basis for catalytic silencing.
  Proteins, 76, 507-511.
PDB code: 2w2j
18451496 A.Sugimoto, H.Ikeda, H.Tsukamoto, K.Kihira, C.Takeda, J.Hirose, T.Hata, E.Baba, and Y.Ono (2008).
The mechanisms by which latanoprost free acid inhibits human carbonic anhydrase I and II.
  Biol Pharm Bull, 31, 796-801.  
18167490 C.T.Supuran (2008).
Carbonic anhydrases: novel therapeutic applications for inhibitors and activators.
  Nat Rev Drug Discov, 7, 168-181.  
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.  
17071654 D.Bhatt, S.Z.Fisher, C.Tu, R.McKenna, and D.N.Silverman (2007).
Location of binding sites in small molecule rescue of human carbonic anhydrase II.
  Biophys J, 92, 562-570.
PDB codes: 2fnk 2fnm 2fnn
17499996 I.Nishimori, S.Onishi, D.Vullo, A.Innocenti, A.Scozzafava, and C.T.Supuran (2007).
Carbonic anhydrase activators: the first activation study of the human secretory isoform VI with amino acids and amines.
  Bioorg Med Chem, 15, 5351-5357.  
17892492 S.Sanchez, A.C.Andersen, S.Hourdez, and F.H.Lallier (2007).
Identification, sequencing, and localization of a new carbonic anhydrase transcript from the hydrothermal vent tubeworm Riftia pachyptila.
  FEBS J, 274, 5311-5324.  
16710859 J.Y.Winum, A.Scozzafava, J.L.Montero, and C.T.Supuran (2006).
Therapeutic potential of sulfamides as enzyme inhibitors.
  Med Res Rev, 26, 767-792.  
20141508 J.Y.Winum, A.Scozzafava, J.L.Montero, and C.T.Supuran (2006).
The sulfamide motif in the design of enzyme inhibitors.
  Expert Opin Ther Pat, 16, 27-47.  
16106378 D.Bhatt, C.Tu, S.Z.Fisher, J.A.Hernandez Prada, R.McKenna, and D.N.Silverman (2005).
Proton transfer in a Thr200His mutant of human carbonic anhydrase II.
  Proteins, 61, 239-245.
PDB codes: 1yo0 1yo1 1yo2
  12930737 B.Knudsen, M.M.Miyamoto, P.J.Laipis, and D.N.Silverman (2003).
Using evolutionary rates to investigate protein functional divergence and conservation. A case study of the carbonic anhydrases.
  Genetics, 164, 1261-1269.  
12500287 C.T.Supuran, A.Scozzafava, and A.Casini (2003).
Carbonic anhydrase inhibitors.
  Med Res Rev, 23, 146-189.  
11863462 H.An, C.Tu, D.Duda, I.Montanez-Clemente, K.Math, P.J.Laipis, R.McKenna, and D.N.Silverman (2002).
Chemical rescue in catalysis by human carbonic anhydrases II and III.
  Biochemistry, 41, 3235-3242.  
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
11327835 D.Duda, C.Tu, M.Qian, P.Laipis, M.Agbandje-McKenna, D.N.Silverman, and R.McKenna (2001).
Structural and kinetic analysis of the chemical rescue of the proton transfer function of carbonic anhydrase II.
  Biochemistry, 40, 1741-1748.
PDB codes: 1g0e 1g0f
11015219 A.Guerri, F.Briganti, A.Scozzafava, C.T.Supuran, and S.Mangani (2000).
Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction.
  Biochemistry, 39, 12391-12397.
PDB code: 1f2w
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.  
10762051 G.Renzi, A.Scozzafava, and C.T.Supuran (2000).
Carbonic anhydrase inhibitors: topical sulfonamide antiglaucoma agents incorporating secondary amine moieties.
  Bioorg Med Chem Lett, 10, 673-676.  
11003159 M.Ilies, C.T.Supuran, A.Scozzafava, A.Casini, F.Mincione, L.Menabuoni, M.T.Caproiu, M.Maganu, and M.D.Banciu (2000).
Carbonic anhydrase inhibitors: sulfonamides incorporating furan-, thiophene- and pyrrole-carboxamido groups possess strong topical intraocular pressure lowering properties as aqueous suspensions.
  Bioorg Med Chem, 8, 2145-2155.  
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.  
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 code is shown on the right.