2f1b: Difference between revisions

Revision as of 03:20, 4 May 2008

GOLGI ALPHA-MANNOSIDASE II COMPLEX WITH (2R,3R,4S,5R)-2-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)-5-methylpyrrolidine-3,4-diol

OverviewOverview

Golgi alpha-mannosidase II (GMII), a zinc-dependent glycosyl hydrolase, is a promising target for drug development in anti-tumor therapies. Using X-ray crystallography, we have determined the structure of Drosophila melanogaster GMII (dGMII) complexed with three different inhibitors exhibiting IC50's ranging from 80 to 1000 microM. These structures, along with those of seven other available dGMII/inhibitor complexes, were then used as a basis for the evaluation of seven docking programs (GOLD, Glide, FlexX, AutoDock, eHiTS, LigandFit, and FITTED). We found that small inhibitors could be accurately docked by most of the software, while docking of larger compounds (i.e., those with extended aromatic cycles or long aliphatic chains) was more problematic. Overall, Glide provided the best docking results, with the most accurately predicted binding around the active site zinc atom. Further evaluation of Glide's performance revealed its ability to extract active compounds from a benchmark library of decoys.

About this StructureAbout this Structure

2F1B is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.

ReferenceReference

Evaluation of docking programs for predicting binding of Golgi alpha-mannosidase II inhibitors: a comparison with crystallography., Englebienne P, Fiaux H, Kuntz DA, Corbeil CR, Gerber-Lemaire S, Rose DR, Moitessier N, Proteins. 2007 Oct 1;69(1):160-76. PMID:17557336 Page seeded by OCA on Sun May 4 03:20:43 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2f1b.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2f1b |SIZE=350|CAPTION= <scene name='initialview01'>2f1b</scene>, resolution 1.45&Aring;
+The line below this paragraph, containing "STRUCTURE_2f1b", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=GB3:(2R,3R,4S,5R)-2-({[(1R)-2-HYDROXY-1-PHENYLETHYL]AMINO}METHYL)-5-METHYLPYRROLIDINE-3,4-DIOL'>GB3</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>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE= alpha-Man-II, GmII ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])
+-->
-|DOMAIN=
+{{STRUCTURE_2f1b|  PDB=2f1b  |  SCENE=  }}
-|RELATEDENTRY=[[1hty|1HTY]], [[1hww|1HWW]], [[1hxk|1HXK]], [[1ps2|1PS2]], [[1qwn|1QWN]], [[1qx1|1QX1]], [[1r33|1R33]], [[1r34|1R34]], [[1tqs|1TQS]], [[1tqt|1TQT]], [[1tqu|1TQU]], [[1tqw|1TQW]], [[2alw|2ALW]], [[2f18|2F18]], [[2f1a|2F1A]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f1b OCA], [http://www.ebi.ac.uk/pdbsum/2f1b PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2f1b RCSB]</span>
-}}
 '''GOLGI ALPHA-MANNOSIDASE II COMPLEX WITH (2R,3R,4S,5R)-2-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)-5-methylpyrrolidine-3,4-diol'''
@@ Line 28: / Line 25: @@
 [[Category: Kuntz, D A.]]
 [[Category: Rose, D R.]]
-[[Category: glycosyl hydrolase family 38]]
+[[Category: Glycosyl hydrolase family 38]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 03:20:43 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:56:31 2008''