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[[Image: | ==Golgi alpha-Mannosidase II in complex with Mannostatin analog (1R,2R,3R,4S,5R)-4-amino-5-methoxycyclopentane-1,2,3-triol== | ||
<StructureSection load='3dx4' size='340' side='right' caption='[[3dx4]], [[Resolution|resolution]] 1.38Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3dx4]] is a 1 chain structure with 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=3DX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DX4 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOO:(1R,2R,3R,4S,5R)-4-AMINO-5-METHOXYCYCLOPENTANE-1,2,3-TRIOL'>GOO</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hty|1hty]], [[1hww|1hww]], [[1hxk|1hxk]], [[1ps2|1ps2]], [[1qwn|1qwn]], [[1r33|1r33]], [[1r34|1r34]], [[1tqv|1tqv]], [[2alw|2alw]], [[2f7o|2f7o]], [[2f7p|2f7p]], [[2f7q|2f7q]], [[2f7r|2f7r]], [[2fyv|2fyv]], [[3bub|3bub]], [[3bup|3bup]], [[3czn|3czn]], [[3dx0|3dx0]], [[3dx1|3dx1]], [[3dx2|3dx2]], [[3dx3|3dx3]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alpha-Man-II, GmII, CG18802 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dx4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dx4 RCSB], [http://www.ebi.ac.uk/pdbsum/3dx4 PDBsum]</span></td></tr> | |||
<table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dx/3dx4_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mannostatin A is a potent inhibitor of the mannose-trimming enzyme, Golgi alpha-mannosidase II (GMII), which acts late in the N-glycan processing pathway. Inhibition of this enzyme provides a route to blocking the transformation-associated changes in cancer cell surface oligosaccharide structures. Here, we report on the synthesis of new Mannostatin derivatives and analyze their binding in the active site of Drosophila GMII by X-ray crystallography. The results indicate that the interaction with the backbone carbonyl of Arg876 is crucial to the high potency of the inhibitor-an effect enhanced by the hydrophobic interaction between the thiomethyl group and an aromatic pocket vicinal to the cleavage site. The various structures indicate that differences in the hydration of protein-ligand complexes are also important determinants of plasticity as well as selectivity of inhibitor binding. | |||
The molecular basis of inhibition of Golgi alpha-mannosidase II by mannostatin A.,Kuntz DA, Zhong W, Guo J, Rose DR, Boons GJ Chembiochem. 2009 Jan 26;10(2):268-77. PMID:19101978<ref>PMID:19101978</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Mannosidase|Mannosidase]] | *[[Mannosidase|Mannosidase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
[[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]] | [[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]] | ||
Revision as of 14:19, 29 September 2014
Golgi alpha-Mannosidase II in complex with Mannostatin analog (1R,2R,3R,4S,5R)-4-amino-5-methoxycyclopentane-1,2,3-triolGolgi alpha-Mannosidase II in complex with Mannostatin analog (1R,2R,3R,4S,5R)-4-amino-5-methoxycyclopentane-1,2,3-triol
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMannostatin A is a potent inhibitor of the mannose-trimming enzyme, Golgi alpha-mannosidase II (GMII), which acts late in the N-glycan processing pathway. Inhibition of this enzyme provides a route to blocking the transformation-associated changes in cancer cell surface oligosaccharide structures. Here, we report on the synthesis of new Mannostatin derivatives and analyze their binding in the active site of Drosophila GMII by X-ray crystallography. The results indicate that the interaction with the backbone carbonyl of Arg876 is crucial to the high potency of the inhibitor-an effect enhanced by the hydrophobic interaction between the thiomethyl group and an aromatic pocket vicinal to the cleavage site. The various structures indicate that differences in the hydration of protein-ligand complexes are also important determinants of plasticity as well as selectivity of inhibitor binding. The molecular basis of inhibition of Golgi alpha-mannosidase II by mannostatin A.,Kuntz DA, Zhong W, Guo J, Rose DR, Boons GJ Chembiochem. 2009 Jan 26;10(2):268-77. PMID:19101978[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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