2GEH

N-Hydroxyurea, a versatile zinc binding function in the design of metalloenzyme inhibitors

Summary for 2GEH

• Entry DOI: 10.2210/pdb2geh/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, MERCURY (II) ION, ... (5 entities in total)
• Functional Keywords: carbonic anhydrase, inhibitors, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29831.71

Authors

Temperini, C.,Innocenti, A.,Scozzafava, A.,Supuran, C.T. (deposition date: 2006-03-20, release date: 2006-06-20, Last modification date: 2024-02-14)

Primary citation

Temperini, C.,Innocenti, A.,Scozzafava, A.,Supuran, C.T.
N-Hydroxyurea-A versatile zinc binding function in the design of metalloenzyme inhibitors.
Bioorg.Med.Chem.Lett., 16:4316-4320, 2006

PubMed Abstract: N-Hydroxyurea binds both to carbonic anhydrase (CA) and to matrix metalloproteinases (MMPs). X-ray crystallography showed N-hydroxyurea to bind in a bidentate mode by means of the oxygen and nitrogen atoms of the NHOH moiety to the Zn(II) ion of CA, participating in a network of hydrogen bonds with a water molecule and Thr199. A derivatized N-hydroxyurea showed low-micromolar affinity for several CAs. This simple zinc binding function may be exploited for obtaining potent metalloenzyme inhibitors, due to its versatility of binding to the metal ion present in the active site of such enzymes.

PubMed: 16759856
DOI: 10.1016/j.bmcl.2006.05.068

Experimental method

X-RAY DIFFRACTION (2 Å)