PDBsum entry 2gd8

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Lyase PDB id
Protein chain
257 a.a. *
PO1 ×2
Waters ×321
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure analysis of the human carbonic anhydrase ii in complex with a 2-substituted estradiol bis-sulfamate
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Ec:
Source: Homo sapiens. Human. Organism_taxid: 9606. Other_details: from human erythrocytes
1.46Å     R-factor:   0.195     R-free:   0.212
Authors: G.De Simone,A.Di Fiore
Key ref: M.P.Leese et al. (2006). 2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity. J Med Chem, 49, 7683-7696. PubMed id: 17181151 DOI: 10.1021/jm060705x
15-Mar-06     Release date:   06-Feb-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
260 a.a.
257 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
= 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/jm060705x J Med Chem 49:7683-7696 (2006)
PubMed id: 17181151  
2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity.
M.P.Leese, B.Leblond, A.Smith, S.P.Newman, A.Di Fiore, G.De Simone, C.T.Supuran, A.Purohit, M.J.Reed, B.V.Potter.
The anticancer activities and SARs of estradiol-17-O-sulfamates and estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS) inhibitors and antiproliferative agents are discussed. Estradiol 3,17-O,O-bis-sulfamates 20 and 21, in contrast to the 17-O-monosulfamate 11, proved to be excellent STS inhibitors. 2-Substituted E2bisMATEs 21 and 23 additionally exhibited potent antiproliferative activity with mean graph midpoint values of 18-87 nM in the NCI 60-cell-line panel. 21 Exhibited antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model, and 23 dosed p.o. caused marked growth inhibition in a nude mouse xenograft tumor model. Modeling studies suggest that the E2bisMATEs and 2-MeOE2 share a common mode of binding to tubulin, though COMPARE analysis of activity profiles was negative. 21 was cocrystallized with carbonic anhydrase II, and X-ray crystallography revealed unexpected coordination of the 17-O-sulfamate of 21 to the active site zinc and a probable additional lower affinity binding site. 2-Substituted E2bisMATEs are attractive candidates for further development as multitargeted anticancer agents.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21244635 A.Stander, F.Joubert, and A.Joubert (2011).
Docking, synthesis, and in vitro evaluation of antimitotic estrone analogs.
  Chem Biol Drug Des, 77, 173-181.  
20029418 C.Stengel, S.P.Newman, M.P.Leese, B.V.Potter, M.J.Reed, and A.Purohit (2010).
Class III beta-tubulin expression and in vitro resistance to microtubule targeting agents.
  Br J Cancer, 102, 316-324.  
19156141 J.M.Day, P.A.Foster, H.J.Tutill, S.P.Newman, Y.T.Ho, M.P.Leese, B.V.Potter, M.J.Reed, and A.Purohit (2009).
BCRP expression does not result in resistance to STX140 in vivo, despite the increased expression of BCRP in A2780 cells in vitro after long-term STX140 exposure.
  Br J Cancer, 100, 476-486.  
18972041 F.Jourdan, C.Bubert, M.P.Leese, A.Smith, E.Ferrandis, S.Regis-Lydi, S.P.Newman, A.Purohit, M.J.Reed, and B.V.Potter (2008).
Effects of C-17 heterocyclic substituents on the anticancer activity of 2-ethylestra-1,3,5(10)-triene-3-O-sulfamates: synthesis, in vitro evaluation and computational modelling.
  Org Biomol Chem, 6, 4108-4119.  
18841154 M.F.Parsons, P.A.Foster, S.K.Chander, R.Jhalli, S.P.Newman, M.P.Leese, B.V.Potter, A.Purohit, and M.J.Reed (2008).
The in vivo properties of STX243: a potent angiogenesis inhibitor in breast cancer.
  Br J Cancer, 99, 1433-1441.  
17957467 P.A.Foster, Y.T.Ho, S.P.Newman, P.G.Kasprzyk, M.P.Leese, B.V.Potter, M.J.Reed, and A.Purohit (2008).
2-MeOE2bisMATE and 2-EtE2bisMATE induce cell cycle arrest and apoptosis in breast cancer xenografts as shown by a novel ex vivo technique.
  Breast Cancer Res Treat, 111, 251-260.  
18985042 S.L.Tagg, P.A.Foster, M.P.Leese, B.V.Potter, M.J.Reed, A.Purohit, and S.P.Newman (2008).
2-Methoxyoestradiol-3,17-O,O-bis-sulphamate and 2-deoxy-D-glucose in combination: a potential treatment for breast and prostate cancer.
  Br J Cancer, 99, 1842-1848.  
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.  
18033583 J.R.Hanson (2007).
Steroids: partial synthesis in medicinal chemistry.
  Nat Prod Rep, 24, 1342-1349.  
17426705 S.K.Chander, P.A.Foster, M.P.Leese, S.P.Newman, B.V.Potter, A.Purohit, and M.J.Reed (2007).
In vivo inhibition of angiogenesis by sulphamoylated derivatives of 2-methoxyoestradiol.
  Br J Cancer, 96, 1368-1376.  
18026194 S.P.Newman, P.A.Foster, Y.T.Ho, J.M.Day, B.Raobaikady, P.G.Kasprzyk, M.P.Leese, B.V.Potter, M.J.Reed, and A.Purohit (2007).
The therapeutic potential of a series of orally bioavailable anti-angiogenic microtubule disruptors as therapy for hormone-independent prostate and breast cancers.
  Br J Cancer, 97, 1673-1682.  
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.