2ow7: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2ow7.jpg|left|200px]] | [[Image:2ow7.jpg|left|200px]] | ||
'''Golgi alpha-mannosidase ii complex with (1R,6S,7R,8S)-1-thioniabicyclo[4.3.0]nonan-7,8-diol chloride''' | {{Structure | ||
|PDB= 2ow7 |SIZE=350|CAPTION= <scene name='initialview01'>2ow7</scene>, resolution 1.770Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene> and <scene name='pdbligand=NK2:'>NK2</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,3-1,6-alpha-mannosidase Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.114 3.2.1.114] | |||
|GENE= | |||
}} | |||
'''Golgi alpha-mannosidase ii complex with (1R,6S,7R,8S)-1-thioniabicyclo[4.3.0]nonan-7,8-diol chloride''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
2OW7 is a [ | 2OW7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OW7 OCA]. | ||
==Reference== | ==Reference== | ||
Binding of sulfonium-ion analogues of di-epi-swainsonine and 8-epi-lentiginosine to Drosophila Golgi alpha-mannosidase II: The role of water in inhibitor binding., Kumar NS, Kuntz DA, Wen X, Pinto BM, Rose DR, Proteins. 2007 Dec 12;. PMID:[http:// | Binding of sulfonium-ion analogues of di-epi-swainsonine and 8-epi-lentiginosine to Drosophila Golgi alpha-mannosidase II: The role of water in inhibitor binding., Kumar NS, Kuntz DA, Wen X, Pinto BM, Rose DR, Proteins. 2007 Dec 12;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18076078 18076078] | ||
[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
[[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]] | [[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]] | ||
| Line 22: | Line 31: | ||
[[Category: glycosyl hydrolase family 38]] | [[Category: glycosyl hydrolase family 38]] | ||
''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 18:05:19 2008'' | ||
Revision as of 19:05, 20 March 2008
| |||||||
| , resolution 1.770Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , and | ||||||
| Activity: | Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase, with EC number 3.2.1.114 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Golgi alpha-mannosidase ii complex with (1R,6S,7R,8S)-1-thioniabicyclo[4.3.0]nonan-7,8-diol chloride
OverviewOverview
Retaining glycosidases operate by a two-step catalytic mechanism in which the transition states are characterized by buildup of a partial positive charge at the anomeric center. Sulfonium-ion analogues of the naturally occurring glycosidase inhibitors, swainsonine and 8-epi-lentiginosine, in which the bridgehead nitrogen atom is replaced by a sulfonium-ion, were synthesized in order to test the hypothesis that a sulfonium salt carrying a permanent positive charge would be an effective glycosidase inhibitor. Initial prediction based on computational docking indicated three plausible binding modes to Drosophila Golgi alpha-mannosidase II (dGMII), the most likely being close to that of swainsonine. Observation of the binding of di-epi-thioswainsonine and 8-epi-thiolentiginosine to dGMII from crystallographic data, however, revealed an orientation different from swainsonine in the active site. Screening these two compounds against dGMII shows that they are inhibitors with IC(50) values of 2.0 and 0.014 mM, respectively. This dramatic difference in affinity between the two compounds, which differ by only one hydroxyl group, is rationalized in terms of bound water molecules and the water molecule substructure in the active site, as identified by comparison of high resolution X-ray crystal structures of several dGMII-inhibitor complexes. Proteins 2007. (c) 2007 Wiley-Liss, Inc.
About this StructureAbout this Structure
2OW7 is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.
ReferenceReference
Binding of sulfonium-ion analogues of di-epi-swainsonine and 8-epi-lentiginosine to Drosophila Golgi alpha-mannosidase II: The role of water in inhibitor binding., Kumar NS, Kuntz DA, Wen X, Pinto BM, Rose DR, Proteins. 2007 Dec 12;. PMID:18076078
Page seeded by OCA on Thu Mar 20 18:05:19 2008