1ze8

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[[Image:1ze8.gif|left|200px]]<br /><applet load="1ze8" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1ze8.gif|left|200px]]
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caption="1ze8, resolution 2.0&Aring;" />
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'''Carbonic anhydrase II in complex with a membrane-impermeant sulfonamide inhibitor'''<br />
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{{Structure
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|PDB= 1ze8 |SIZE=350|CAPTION= <scene name='initialview01'>1ze8</scene>, resolution 2.0&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=HGB:4-(HYDROXYMERCURY)BENZOIC+ACID'>HGB</scene>, <scene name='pdbligand=PIU:1-{2-[4-(AMINOSULFONYL)PHENYL]ETHYL}-2,4,6-TRIMETHYLPYRIDINIUM'>PIU</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
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|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]
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|GENE=
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}}
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'''Carbonic anhydrase II in complex with a membrane-impermeant sulfonamide inhibitor'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1ZE8 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=HGB:'>HGB</scene>, <scene name='pdbligand=PIU:'>PIU</scene> and <scene name='pdbligand=GOL:'>GOL</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=1ZE8 OCA].
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1ZE8 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=1ZE8 OCA].
==Reference==
==Reference==
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Carbonic anhydrase inhibitors: stacking with Phe131 determines active site binding region of inhibitors as exemplified by the X-ray crystal structure of a membrane-impermeant antitumor sulfonamide complexed with isozyme II., Menchise V, De Simone G, Alterio V, Di Fiore A, Pedone C, Scozzafava A, Supuran CT, J Med Chem. 2005 Sep 8;48(18):5721-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16134940 16134940]
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Carbonic anhydrase inhibitors: stacking with Phe131 determines active site binding region of inhibitors as exemplified by the X-ray crystal structure of a membrane-impermeant antitumor sulfonamide complexed with isozyme II., Menchise V, De Simone G, Alterio V, Di Fiore A, Pedone C, Scozzafava A, Supuran CT, J Med Chem. 2005 Sep 8;48(18):5721-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16134940 16134940]
[[Category: Carbonate dehydratase]]
[[Category: Carbonate dehydratase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: twisted beta-sheet]]
[[Category: twisted beta-sheet]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:14:41 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:34:24 2008''

Revision as of 13:34, 20 March 2008

Image:1ze8.gif


PDB ID 1ze8

Drag the structure with the mouse to rotate
, resolution 2.0Å
Ligands: , , and
Activity: Carbonate dehydratase, with EC number 4.2.1.1
Coordinates: save as pdb, mmCIF, xml



Carbonic anhydrase II in complex with a membrane-impermeant sulfonamide inhibitor


Contents

Overview

Structure for the adduct of carbonic anhydrase II with 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate, a membrane-impermeant antitumor sulfonamide, is reported. The phenylethyl moiety fills the active site, making van der Waals interactions with side chains of Gln192, Val121, Phe131, Leu198, Thr200. The 2,4,6-trimethylpyridinium functionality is at van der Waals distance from the aliphatic chain of Ile91 being involved in strong offset face-to-face stacking with Phe131. Analyzing X-ray crystal structures of such adducts, two binding modes were observed: some inhibitors bind with their tail within the hydrophobic half of the active site, defined by residues Phe131, Val135, Leu198, Pro202, Leu204. Other derivatives bind with their tail in a different region, pointing toward the hydrophilic half and making strong parallel stacking with Phe131. This interaction orients the inhibitor toward the hydrophilic part of the active site. Impossibility to participate in it leads to its binding within the hydrophobic half. Such findings are relevant for designing better inhibitors targeting isozymes II, IX, and XII, some of which are overexpressed in hypoxic tumors.

Disease

Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]

About this Structure

1ZE8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Carbonic anhydrase inhibitors: stacking with Phe131 determines active site binding region of inhibitors as exemplified by the X-ray crystal structure of a membrane-impermeant antitumor sulfonamide complexed with isozyme II., Menchise V, De Simone G, Alterio V, Di Fiore A, Pedone C, Scozzafava A, Supuran CT, J Med Chem. 2005 Sep 8;48(18):5721-7. PMID:16134940

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