2q1q
From Proteopedia
(New page: 200px<br /> <applet load="2q1q" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q1q, resolution 1.90Å" /> '''Carbonic anhydrase ...) |
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caption="2q1q, resolution 1.90Å" /> | caption="2q1q, resolution 1.90Å" /> | ||
'''Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies'''<br /> | '''Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies'''<br /> | ||
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==Overview== | ==Overview== | ||
Sulthiame, a clinically used antiepileptic, was investigated for its, interaction with 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms. The drug is a potent inhibitor of CA II, VII, IX, and XII (K(I)s of 6-56nM), and a medium potency inhibitor against CA IV, VA, VB, and VI (K(I)s of 81-134nM). The high resolution crystal structure, of the hCA II-sulthiame adduct revealed a large number of favorable, interactions between the drug and the enzyme which explain its strong low, nanomolar affinity for this isoform and may also be exploited for the, design of effective inhibitors incorporating sultam moieties. | Sulthiame, a clinically used antiepileptic, was investigated for its, interaction with 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms. The drug is a potent inhibitor of CA II, VII, IX, and XII (K(I)s of 6-56nM), and a medium potency inhibitor against CA IV, VA, VB, and VI (K(I)s of 81-134nM). The high resolution crystal structure, of the hCA II-sulthiame adduct revealed a large number of favorable, interactions between the drug and the enzyme which explain its strong low, nanomolar affinity for this isoform and may also be exploited for the, design of effective inhibitors incorporating sultam moieties. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611492 611492]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2Q1Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with ZN, HG and OSP 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:// | + | 2Q1Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HG:'>HG</scene> and <scene name='pdbligand=OSP:'>OSP</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=2Q1Q OCA]. |
==Reference== | ==Reference== | ||
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[[Category: lyase]] | [[Category: lyase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:40:16 2008'' |
Revision as of 11:40, 23 January 2008
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Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies
Overview
Sulthiame, a clinically used antiepileptic, was investigated for its, interaction with 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms. The drug is a potent inhibitor of CA II, VII, IX, and XII (K(I)s of 6-56nM), and a medium potency inhibitor against CA IV, VA, VB, and VI (K(I)s of 81-134nM). The high resolution crystal structure, of the hCA II-sulthiame adduct revealed a large number of favorable, interactions between the drug and the enzyme which explain its strong low, nanomolar affinity for this isoform and may also be exploited for the, design of effective inhibitors incorporating sultam moieties.
About this Structure
2Q1Q is a Single protein structure of sequence from [1] with , and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: Kinetic and X-ray crystallographic studies., Temperini C, Innocenti A, Mastrolorenzo A, Scozzafava A, Supuran CT, Bioorg Med Chem Lett. 2007 Sep 1;17(17):4866-72. Epub 2007 Jun 14. PMID:17588751
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