2iuz
From Proteopedia
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|PDB= 2iuz |SIZE=350|CAPTION= <scene name='initialview01'>2iuz</scene>, resolution 1.95Å | |PDB= 2iuz |SIZE=350|CAPTION= <scene name='initialview01'>2iuz</scene>, resolution 1.95Å | ||
|SITE= <scene name='pdbsite=AC1:D1h+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:D1h+Binding+Site+For+Chain+B'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=D1H:1,1 | + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=D1H:1,1'-ETHANE-1,2-DIYLBIS(3,7-DIMETHYL-3,7-DIHYDRO-1H-PURINE-2,6-DIONE)'>D1H</scene> |
|ACTIVITY= [http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] | |ACTIVITY= [http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] | ||
|GENE= | |GENE= | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 15:22:39 2008'' |
Revision as of 13:22, 23 March 2008
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| , resolution 1.95Å | |||||||
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| Sites: | |||||||
| Ligands: | and | ||||||
| Activity: | Chitinase, with EC number 3.2.1.14 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF ASPERGILLUS FUMIGATUS CHITINASE B1 IN COMPLEX WITH C2-DICAFFEINE
Overview
Family 18 chitinases play key roles in the life cycles of a variety of organisms ranging from bacteria to man. Very recently it has been shown that one of the mammalian chitinases is highly overexpressed in the asthmatic lung and contributes to the pathogenic process through recruitment of inflammatory cells. Although several potent natural product chitinase inhibitors have been identified, their chemotherapeutic potential or their use as cell biological tools is limited due to their size, complex chemistry, and limited availability. We describe a virtual screening-based approach to identification of a novel, purine-based, chitinase inhibitor. This inhibitor acts in the low micromolar (Ki=2.8+/-0.2 microM) range in a competitive mode. Dissection of the binding mode by x-ray crystallography reveals that the compound, which consists of two linked caffeine moieties, binds in the active site through extensive and not previously observed stacking interactions with conserved, solvent exposed tryptophans. Such exposed aromatics are also present in the structures of many other carbohydrate processing enzymes. The compound exhibits favorable chemical properties and is likely to be useful as a general scaffold for development of pan-family 18 chitinase inhibitors.
About this Structure
2IUZ is a Single protein structure of sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA.
Reference
Screening-based discovery and structural dissection of a novel family 18 chitinase inhibitor., Schuttelkopf AW, Andersen OA, Rao FV, Allwood M, Lloyd C, Eggleston IM, van Aalten DM, J Biol Chem. 2006 Sep 15;281(37):27278-85. Epub 2006 Jul 14. PMID:16844689
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