PDBsum entry 4g0c

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Lyase/lyase inhibitor PDB id
Protein chain
257 a.a.
DOD ×142
PDB id:
Name: Lyase/lyase inhibitor
Title: Neutron structure of acetazolamide-bound human carbonic anhy reveal molecular details of drug binding.
Structure: Carbonic anhydrase 2. Chain: a. Fragment: hca ii. Synonym: carbonate dehydratase ii, carbonic anhydrasE C, ca carbonic anhydrase ii, ca-ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Authors: S.Z.Fisher, Mckenna,R.,M.Aggarwal
Key ref: S.Z.Fisher et al. (2012). Neutron diffraction of acetazolamide-bound human carbonic anhydrase II reveals atomic details of drug binding. J Am Chem Soc, 134, 14726-14729. PubMed id: 22928733
09-Jul-12     Release date:   19-Sep-12    
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: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   9 terms 
  Biological process     angiotensin-mediated signaling pathway   20 terms 
  Biochemical function     protein binding     5 terms  


    Added reference    
J Am Chem Soc 134:14726-14729 (2012)
PubMed id: 22928733  
Neutron diffraction of acetazolamide-bound human carbonic anhydrase II reveals atomic details of drug binding.
S.Z.Fisher, M.Aggarwal, A.Y.Kovalevsky, D.N.Silverman, R.McKenna.
Carbonic anhydrases (CAs) catalyze the hydration of CO(2) forming HCO(3)(-) and a proton, an important reaction for many physiological processes including respiration, fluid secretion, and pH regulation. As such, CA isoforms are prominent clinical targets for treating various diseases. The clinically used acetazolamide (AZM) is a sulfonamide that binds with high affinity to human CA isoform II (HCA II). There are several X-ray structures available of AZM bound to various CA isoforms, but these complexes do not show the charged state of AZM or the hydrogen atom positions of the protein and solvent. Neutron diffraction is a useful technique for directly observing H atoms and the mapping of H-bonding networks that can greatly contribute to rational drug design. To this end, the neutron structure of H/D exchanged HCA II crystals in complex with AZM was determined. The structure reveals the molecular details of AZM binding and the charged state of the bound drug. This represents the first determined neutron structure of a clinically used drug bound to its target.