2f7p
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 2f7p |SIZE=350|CAPTION= <scene name='initialview01'>2f7p</scene>, resolution 1.280Å | |PDB= 2f7p |SIZE=350|CAPTION= <scene name='initialview01'>2f7p</scene>, resolution 1.280Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=2SK:(1R,2R,3R,4S,5R)-4-(BENZYLAMINO)-5-(METHYLTHIO)CYCLOPENTANE-1,2,3-TRIOL'>2SK</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= alpha-Man-II, GmII ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster]) | |GENE= alpha-Man-II, GmII ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1hty|1HTY]], [[1hww|1HWW]], [[1hxk|1HXK]], [[1ps3|1PS3]], [[1qwn|1QWN]], [[1qwu|1QWU]], [[1qx1|1QX1]], [[2f7o|2F7O]], [[2f7q|2F7Q]], [[2f7r|2F7R]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f7p OCA], [http://www.ebi.ac.uk/pdbsum/2f7p PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2f7p RCSB]</span> | ||
}} | }} | ||
| Line 25: | Line 28: | ||
[[Category: Kuntz, D A.]] | [[Category: Kuntz, D A.]] | ||
[[Category: Rose, D R.]] | [[Category: Rose, D R.]] | ||
| - | [[Category: 2SK]] | ||
| - | [[Category: MPD]] | ||
| - | [[Category: NAG]] | ||
| - | [[Category: ZN]] | ||
[[Category: glycosyl hydrolase family 38]] | [[Category: glycosyl hydrolase family 38]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:59:01 2008'' |
Revision as of 23:59, 30 March 2008
| |||||||
| , resolution 1.280Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Gene: | alpha-Man-II, GmII (Drosophila melanogaster) | ||||||
| Activity: | Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase, with EC number 3.2.1.114 | ||||||
| Related: | 1HTY, 1HWW, 1HXK, 1PS3, 1QWN, 1QWU, 1QX1, 2F7O, 2F7Q, 2F7R
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Golgi alpha-mannosidase II complex with benzyl-mannostatin A
Overview
The X-ray crystal structures of mannose trimming enzyme drosophila Golgi alpha-mannosidase II (dGMII) complexed with the inhibitors mannostatin A (1) and an N-benzyl analogue (2) have been determined. Molecular dynamics simulations and NMR studies have shown that the five-membered ring of mannostatin A is rather flexible occupying pseudorotational itineraries between 2T3 and 5E, and 2T3 and 4E. In the bound state, mannostatin A adopts a 2T1 twist envelope conformation, which is not significantly populated in solution. Possible conformations of the mannosyl oxacarbenium ion and an enzyme-linked intermediate have been compared to the conformation of mannostatin A in the cocrystal structure with dGMII. It has been found that mannostatin A best mimics the covalent linked mannosyl intermediate, which adopts a 1S5 skew boat conformation. The thiomethyl group, which is critical for high affinity, superimposes with the C-6 hydroxyl of the covalent linked intermediate. This functionality is able to make a number of additional polar and nonpolar interactions increasing the affinity for dGMII. Furthermore, the X-ray structures show that the environment surrounding the thiomethyl group of 1 is remarkably similar to the arrangements around the methionine residues in the protein. Collectively, our studies contradict the long held view that potent inhibitors of glycosidases must mimic an oxacarbenium ion like transition state.
About this Structure
2F7P is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.
Reference
Structural basis of the inhibition of Golgi alpha-mannosidase II by mannostatin A and the role of the thiomethyl moiety in ligand-protein interactions., Kawatkar SP, Kuntz DA, Woods RJ, Rose DR, Boons GJ, J Am Chem Soc. 2006 Jun 28;128(25):8310-9. PMID:16787095
Page seeded by OCA on Mon Mar 31 02:59:01 2008
