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PDBsum entry 2wd2

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protein ligands metals links
Lyase PDB id
2wd2
Jmol
Contents
Protein chain
254 a.a. *
Ligands
MS5
FMT ×3
Metals
_ZN ×2
Waters ×245
* Residue conservation analysis
PDB id:
2wd2
Name: Lyase
Title: A chimeric microtubule disruptor with efficacy on a taxane resistant cell line
Structure: Carbonic anhydrase 2. Chain: a. Fragment: residues 2-260. Synonym: carbonate dehydratase ii, carbonic anhydrasE C, ca-ii, caccarbonic anhydrase ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
1.49Å     R-factor:   0.206     R-free:   0.227
Authors: M.P.Leese,F.L.Jourdan,M.R.Kimberley,G.E.Cozier,S.Regis-Lydi, P.A.Foster,S.P.Newman,N.Thiyagarajan,K.R.Acharya, E.Ferrandis,A.Purohit,M.J.Reed,B.V.L.Potter
Key ref: M.P.Leese et al. (2010). Chimeric microtubule disruptors. Chem Commun (Camb), 46, 2907-2909. PubMed id: 20386818 DOI: 10.1039/c002558e
Date:
19-Mar-09     Release date:   31-Mar-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
254 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)
Bound ligand (Het Group name = FMT)
corresponds exactly
+ H(2)O
      Cofactor: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   10 terms 
  Biological process     angiotensin-mediated signaling pathway   20 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1039/c002558e Chem Commun (Camb) 46:2907-2909 (2010)
PubMed id: 20386818  
 
 
Chimeric microtubule disruptors.
M.P.Leese, F.Jourdan, M.R.Kimberley, G.E.Cozier, N.Thiyagarajan, C.Stengel, S.Regis-Lydi, P.A.Foster, S.P.Newman, K.R.Acharya, E.Ferrandis, A.Purohit, M.J.Reed, B.V.Potter.
 
  ABSTRACT  
 
A chimeric approach is used to discover microtubule disruptors with excellent in vitro activity and oral bioavailability; a ligand-protein interaction with carbonic anhydrase that enhances bioavailability is characterised by protein X-ray crystallography. Dosing of a representative chimera in a tumour xenograft model confirms the excellent therapeutic potential of the class.