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PDBsum entry 2fov

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protein ligands metals links
Lyase PDB id
2fov
Jmol
Contents
Protein chain
259 a.a. *
Ligands
B30 ×2
CCN
Metals
_ZN
_CU
Waters ×269
* Residue conservation analysis
PDB id:
2fov
Name: Lyase
Title: Human carbonic anhydrase ii complexed with two-prong inhibitors
Structure: Carbonic anhydrase ii. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.15Å     R-factor:   0.143     R-free:   0.187
Authors: K.M.Jude,D.W.Christianson
Key ref: K.M.Jude et al. (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. PubMed id: 16506782 DOI: 10.1021/ja057257n
Date:
14-Jan-06     Release date:   04-Apr-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
259 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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/ja057257n J Am Chem Soc 128:3011-3018 (2006)
PubMed id: 16506782  
 
 
Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors reveal the molecular basis of high affinity.
K.M.Jude, A.L.Banerjee, M.K.Haldar, S.Manokaran, B.Roy, S.Mallik, D.K.Srivastava, D.W.Christianson.
 
  ABSTRACT  
 
The atomic-resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors are reported. Each inhibitor contains a benzenesulfonamide prong and a cupric iminodiacetate (IDA-Cu(2+)) prong separated by linkers of different lengths and compositions. The ionized NH(-) group of each benzenesulfonamide coordinates to the active site Zn(2+) ion; the IDA-Cu(2+) prong of the tightest-binding inhibitor, BR30, binds to H64 of CAII and H200 of CAI. This work provides the first evidence verifying the structural basis of nanomolar affinity measured for two-prong inhibitors targeting the carbonic anhydrases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20445237 C.A.Behnke, I.Le Trong, J.W.Godden, E.A.Merritt, D.C.Teller, J.Bajorath, and R.E.Stenkamp (2010).
Atomic resolution studies of carbonic anhydrase II.
  Acta Crystallogr D Biol Crystallogr, 66, 616-627.
PDB codes: 1lug 3k34
20505865 V.Alterio, S.M.Monti, E.Truppo, C.Pedone, C.T.Supuran, and G.De Simone (2010).
The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex.
  Org Biomol Chem, 8, 3528-3533.
PDB code: 3lxe
19225621 E.Meggers (2009).
Targeting proteins with metal complexes.
  Chem Commun (Camb), (), 1001-1010.  
  19851004 K.H.Sippel, A.H.Robbins, J.Domsic, C.Genis, M.Agbandje-McKenna, and R.McKenna (2009).
High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 992-995.
PDB code: 3hs4
19715312 K.L.Haas, and K.J.Franz (2009).
Application of metal coordination chemistry to explore and manipulate cell biology.
  Chem Rev, 109, 4921-4960.  
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.  
18019504 A.I.Elegbede, M.K.Haldar, S.Manokaran, J.Kooren, B.C.Roy, S.Mallik, and D.K.Srivastava (2007).
A strategy for designing "multi-prong" enzyme inhibitors by incorporating selective ligands to the liposomal surface.
  Chem Commun (Camb), (), 3377-3379.  
17971967 A.I.Elegbede, M.K.Haldar, S.Manokaran, S.Mallik, and D.K.Srivastava (2007).
Recognition of isozymes via lanthanide ion incorporated polymerized liposomes.
  Chem Commun (Camb), (), 4495-4497.  
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
17163561 F.E.Jacobsen, J.A.Lewis, and S.M.Cohen (2007).
The Design of Inhibitors for Medicinally Relevant Metalloproteins.
  ChemMedChem, 2, 152-171.  
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.  
17084612 D.A.Erlanson (2006).
Fragment-based lead discovery: a chemical update.
  Curr Opin Biotechnol, 17, 643-652.  
17176043 H.A.Gennadios, and D.W.Christianson (2006).
Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase LpxC and implications for substrate binding.
  Biochemistry, 45, 15216-15223.
PDB codes: 2ier 2ies
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.