1eou
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | The fructose-based sugar sulphamate RWJ-37497, a potent analogue of the | + | The fructose-based sugar sulphamate RWJ-37497, a potent analogue of the widely used anti-epileptic drug topiramate, possesses anti-convulsant and carbonic anhydrase-inhibitory activities. We have studied the binding interactions of RWJ-37497 in the active site of human carbonic anhydrase II by X-ray crystallography. The atomic positions of the enzyme inhibitor complex were refined at a resolution of 2.1 A (1 A=0.1 nm) to the final crystallographic R and R(free) values of 0.18 and 0.23, respectively. The inhibitor co-ordinates to the active-site zinc ion through its oxygen atom and the ionized nitrogen atom of the sulphamate group by replacing the metal-bound water molecules, although the sulphamoyl oxygen atom provides a rather lengthy co-ordination. The 4,5-cyclic sulphate group is positioned in a hydrophobic pocket of the active site, making contacts with the residues Phe-131, Leu-198, Pro-201 and Pro-202. Since the ligand was found to be intact, concerns about RWJ-37947 irreversibly alkylating the enzyme through its 4,5-cyclic sulphate group were dispelled. |
==Disease== | ==Disease== | ||
| Line 18: | Line 18: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chattopadhyay, D.]] | [[Category: Chattopadhyay, D.]] | ||
| - | [[Category: Costanzo, M | + | [[Category: Costanzo, M J.]] |
| - | [[Category: Maryanoff, B | + | [[Category: Maryanoff, B E.]] |
[[Category: Recacha, R.]] | [[Category: Recacha, R.]] | ||
[[Category: SMS]] | [[Category: SMS]] | ||
| Line 27: | Line 27: | ||
[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:30:00 2008'' |
Revision as of 10:30, 21 February 2008
|
CRYSTAL STRUCTURE OF HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH AN ANTICONVULSANT SUGAR SULFAMATE
Contents |
Overview
The fructose-based sugar sulphamate RWJ-37497, a potent analogue of the widely used anti-epileptic drug topiramate, possesses anti-convulsant and carbonic anhydrase-inhibitory activities. We have studied the binding interactions of RWJ-37497 in the active site of human carbonic anhydrase II by X-ray crystallography. The atomic positions of the enzyme inhibitor complex were refined at a resolution of 2.1 A (1 A=0.1 nm) to the final crystallographic R and R(free) values of 0.18 and 0.23, respectively. The inhibitor co-ordinates to the active-site zinc ion through its oxygen atom and the ionized nitrogen atom of the sulphamate group by replacing the metal-bound water molecules, although the sulphamoyl oxygen atom provides a rather lengthy co-ordination. The 4,5-cyclic sulphate group is positioned in a hydrophobic pocket of the active site, making contacts with the residues Phe-131, Leu-198, Pro-201 and Pro-202. Since the ligand was found to be intact, concerns about RWJ-37947 irreversibly alkylating the enzyme through its 4,5-cyclic sulphate group were dispelled.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
1EOU 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
Crystal structure of human carbonic anhydrase II complexed with an anti-convulsant sugar sulphamate., Recacha R, Costanzo MJ, Maryanoff BE, Chattopadhyay D, Biochem J. 2002 Feb 1;361(Pt 3):437-41. PMID:11802772
Page seeded by OCA on Thu Feb 21 12:30:00 2008
