2o4z: Difference between revisions
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[[Image:2o4z.gif|left|200px]] | [[Image:2o4z.gif|left|200px]] | ||
'''Crystal structure of the Carbonic Anhydrase II complexed with hydroxysulfamide inhibitor''' | {{Structure | ||
|PDB= 2o4z |SIZE=350|CAPTION= <scene name='initialview01'>2o4z</scene>, resolution 2.10Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene> and <scene name='pdbligand=HSW:N-hydroxysulfamide'>HSW</scene> | |||
|ACTIVITY= [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] | |||
|GENE= | |||
}} | |||
'''Crystal structure of the Carbonic Anhydrase II complexed with hydroxysulfamide inhibitor''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2O4Z is a [ | 2O4Z is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O4Z OCA]. | ||
==Reference== | ==Reference== | ||
Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors., Temperini C, Winum JY, Montero JL, Scozzafava A, Supuran CT, Bioorg Med Chem Lett. 2007 May 15;17(10):2795-801. Epub 2007 Feb 28. PMID:[http:// | Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors., Temperini C, Winum JY, Montero JL, Scozzafava A, Supuran CT, Bioorg Med Chem Lett. 2007 May 15;17(10):2795-801. Epub 2007 Feb 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17346964 17346964] | ||
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: carbonic anhydrase]] | [[Category: carbonic anhydrase]] | ||
[[Category: crystal structure]] | [[Category: crystal structure]] | ||
[[Category: | [[Category: inhibitor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:55:07 2008'' | ||
Revision as of 18:55, 20 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Carbonate dehydratase, with EC number 4.2.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the Carbonic Anhydrase II complexed with hydroxysulfamide inhibitor
OverviewOverview
N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also inhibits other physiologically relevant isoforms, such as the tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34microM). In order to understand the binding of this inhibitor to the enzyme active site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide adduct was resolved. The inhibitor coordinates to the active site zinc ion by the ionized primary amino group, participating in an extended network of hydrogen bonds with amino acid residues Thr199, Thr200 and two water molecules. The additional two hydrogen bonds in which N-hydroxysulfamide bound to hCA II is involved as compared to the corresponding adduct of sulfamide may explain its higher affinity for the enzyme, also providing hints for the design of tight-binding CA inhibitors possessing an organic moiety substituting the NH group in the N-hydroxysulfamide structure.
DiseaseDisease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this StructureAbout this Structure
2O4Z is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors., Temperini C, Winum JY, Montero JL, Scozzafava A, Supuran CT, Bioorg Med Chem Lett. 2007 May 15;17(10):2795-801. Epub 2007 Feb 28. PMID:17346964
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