2geh
From Proteopedia
(New page: 200px<br /> <applet load="2geh" size="450" color="white" frame="true" align="right" spinBox="true" caption="2geh, resolution 2.0Å" /> '''N-Hydroxyurea, a ver...) |
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| - | [[Image:2geh.gif|left|200px]]<br /> | + | [[Image:2geh.gif|left|200px]]<br /><applet load="2geh" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2geh" size=" | + | |
caption="2geh, resolution 2.0Å" /> | caption="2geh, resolution 2.0Å" /> | ||
'''N-Hydroxyurea, a versatile zinc binding function in the design of metalloenzyme inhibitors'''<br /> | '''N-Hydroxyurea, a versatile zinc binding function in the design of metalloenzyme inhibitors'''<br /> | ||
==Overview== | ==Overview== | ||
| - | N-Hydroxyurea binds both to carbonic anhydrase (CA) and to matrix | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2GEH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, HG and NHY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http:// | + | 2GEH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HG:'>HG</scene> and <scene name='pdbligand=NHY:'>NHY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GEH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Innocenti, A.]] | [[Category: Innocenti, A.]] | ||
[[Category: Scozzafava, A.]] | [[Category: Scozzafava, A.]] | ||
| - | [[Category: Supuran, C | + | [[Category: Supuran, C T.]] |
[[Category: Temperini, C.]] | [[Category: Temperini, C.]] | ||
[[Category: HG]] | [[Category: HG]] | ||
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[[Category: inhibitors]] | [[Category: inhibitors]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:30:54 2008'' |
Revision as of 15:30, 21 February 2008
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N-Hydroxyurea, a versatile zinc binding function in the design of metalloenzyme inhibitors
Contents |
Overview
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.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
2GEH is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
N-hydroxyurea--a versatile zinc binding function in the design of metalloenzyme inhibitors., Temperini C, Innocenti A, Scozzafava A, Supuran CT, Bioorg Med Chem Lett. 2006 Aug 15;16(16):4316-20. Epub 2006 Jun 12. PMID:16759856
Page seeded by OCA on Thu Feb 21 17:30:54 2008
