3ejq: Difference between revisions
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< | ==Golgi alpha-Mannosidase II in complex with 5-substitued swainsonine analog: (5R)-5-[2'-oxo-2'-(4-methylphenyl)ethyl]-swainsonine== | ||
<StructureSection load='3ejq' size='340' side='right'caption='[[3ejq]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
You may | == Structural highlights == | ||
or the | <table><tr><td colspan='2'>[[3ejq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EJQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EJQ FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HN3:1-(4-METHYLPHENYL)-2-[(1S,2R,5R,8R,8AR)-1,2,8-TRIHYDROXYOCTAHYDROINDOLIZIN-5-YL]ETHANONE'>HN3</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></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ejq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ejq OCA], [https://pdbe.org/3ejq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ejq RCSB], [https://www.ebi.ac.uk/pdbsum/3ejq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ejq ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MAN2_DROME MAN2_DROME] Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway (By similarity). | |||
== 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/ej/3ejq_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=3ejq ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Golgi alpha-mannosidase II (GMII) is a key enzyme in the N-glycosylation pathway and is a potential target for cancer chemotherapy. The natural product swainsonine is a potent inhibitor of GMII. In this paper we characterize the binding of 5alpha-substituted swainsonine analogues to the soluble catalytic domain of Drosophila GMII by X-ray crystallography. These inhibitors enjoy an advantage over previously reported GMII inhibitors in that they did not significantly decrease the inhibitory potential of the swainsonine head-group. The phenyl groups of these analogues occupy a portion of the binding site not previously seen to be populated with either substrate analogues or other inhibitors and they form novel hydrophobic interactions. They displace a well-organized water cluster, but the presence of a C(10) carbonyl allows the reestablishment of important hydrogen bonds. Already approximately tenfold more active against the Golgi enzyme than the lysosomal enzyme, these inhibitors offer the potential of being extended into the N-acetylglucosamine binding site of GMII for the creation of even more potent and selective GMII inhibitors. | |||
Structural Investigation of the Binding of 5-Substituted Swainsonine Analogues to Golgi alpha-Mannosidase II.,Kuntz DA, Nakayama S, Shea K, Hori H, Uto Y, Nagasawa H, Rose DR Chembiochem. 2010 Mar 5;11(5):673-680. PMID:20209559<ref>PMID:20209559</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ejq" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Mannosidase 3D structures|Mannosidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Kuntz | [[Category: Kuntz DA]] | ||
[[Category: Rose | [[Category: Rose DR]] | ||
Latest revision as of 08:47, 17 October 2024
Golgi alpha-Mannosidase II in complex with 5-substitued swainsonine analog: (5R)-5-[2'-oxo-2'-(4-methylphenyl)ethyl]-swainsonineGolgi alpha-Mannosidase II in complex with 5-substitued swainsonine analog: (5R)-5-[2'-oxo-2'-(4-methylphenyl)ethyl]-swainsonine
Structural highlights
FunctionMAN2_DROME Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway (By similarity). 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 PubMedGolgi alpha-mannosidase II (GMII) is a key enzyme in the N-glycosylation pathway and is a potential target for cancer chemotherapy. The natural product swainsonine is a potent inhibitor of GMII. In this paper we characterize the binding of 5alpha-substituted swainsonine analogues to the soluble catalytic domain of Drosophila GMII by X-ray crystallography. These inhibitors enjoy an advantage over previously reported GMII inhibitors in that they did not significantly decrease the inhibitory potential of the swainsonine head-group. The phenyl groups of these analogues occupy a portion of the binding site not previously seen to be populated with either substrate analogues or other inhibitors and they form novel hydrophobic interactions. They displace a well-organized water cluster, but the presence of a C(10) carbonyl allows the reestablishment of important hydrogen bonds. Already approximately tenfold more active against the Golgi enzyme than the lysosomal enzyme, these inhibitors offer the potential of being extended into the N-acetylglucosamine binding site of GMII for the creation of even more potent and selective GMII inhibitors. Structural Investigation of the Binding of 5-Substituted Swainsonine Analogues to Golgi alpha-Mannosidase II.,Kuntz DA, Nakayama S, Shea K, Hori H, Uto Y, Nagasawa H, Rose DR Chembiochem. 2010 Mar 5;11(5):673-680. PMID:20209559[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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