PDBsum entry 3bet

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Lyase PDB id
Protein chain
258 a.a. *
Waters ×292
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure of the human carbonic anhydrase ii in comp stx 641 at 1.85 angstroms resolution
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, c carbonic anhydrasE C. Ec:
Source: Homo sapiens. Human. Organism_taxid: 9606
1.85Å     R-factor:   0.170     R-free:   0.203
Authors: A.Di Fiore,G.De Simone
Key ref: M.P.Leese et al. (2008). Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents. J Med Chem, 51, 1295-1308. PubMed id: 18260615 DOI: 10.1021/jm701319c
20-Nov-07     Release date:   07-Oct-08    
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Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
260 a.a.
258 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/jm701319c J Med Chem 51:1295-1308 (2008)
PubMed id: 18260615  
Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents.
M.P.Leese, F.L.Jourdan, K.Gaukroger, M.F.Mahon, S.P.Newman, P.A.Foster, C.Stengel, S.Regis-Lydi, E.Ferrandis, A.Di Fiore, G.De Simone, C.T.Supuran, A.Purohit, M.J.Reed, B.V.Potter.
The synthesis, SAR, and preclinical evaluation of 17-cyanated 2-substituted estra-1,3,5(10)-trienes as anticancer agents are discussed. 2-Methoxy-17beta-cyanomethylestra-1,3,5(10)-trien-3-ol ( 14), but not the related 2-ethyl derivative 7, and the related 3- O-sulfamates 8 and 15 display potent antiproliferative effects (MCF-7 GI 50 300, 60 and 70 nM, respectively) against human cancer cells in vitro. Investigation of the SAR reveals that a sterically unhindered hydrogen bond acceptor attached to C-17 is most likely key to the enhanced activity. Compound 8 displayed significant in vitro antiangiogenic activity, and its ability to act as a microtubule disruptor was confirmed. Inhibitory activity of the sulfamate derivatives against steroid sulfatase and carbonic anhydrase II (hCAII) was also observed, and the interaction between 15 and hCAII was investigated by protein crystallography. The potential of these multimechanism anticancer agents was confirmed in vivo, with promising activity observed for both 14 and 15 in an athymic nude mouse MDA-MB-231 human breast cancer xenograft model.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20424788 J.R.Hanson (2010).
Steroids: partial synthesis in medicinal chemistry.
  Nat Prod Rep, 27, 887-899.  
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.  
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