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| - | [[Image:2fyv.jpg|left|200px]] | |
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| - | {{Structure
| + | ==Golgi alpha-mannosidase II complex with an amino-salacinol carboxylate analog== |
| - | |PDB= 2fyv |SIZE=350|CAPTION= <scene name='initialview01'>2fyv</scene>, resolution 1.900Å
| + | <StructureSection load='2fyv' size='340' side='right'caption='[[2fyv]], [[Resolution|resolution]] 1.90Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=W72:6-DEOXY-6-[(2R,3R,4R)-3,4-DIHYDROXY-2-(HYDROXYMETHYL)PYRROLIDIN-1-YL]-L-GULONIC+ACID'>W72</scene> and <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene> | + | <table><tr><td colspan='2'>[[2fyv]] 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=2FYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FYV FirstGlance]. <br> |
| - | |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]
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=W72:6-DEOXY-6-[(2R,3R,4R)-3,4-DIHYDROXY-2-(HYDROXYMETHYL)PYRROLIDIN-1-YL]-L-GULONIC+ACID'>W72</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=2fyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fyv OCA], [https://pdbe.org/2fyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fyv RCSB], [https://www.ebi.ac.uk/pdbsum/2fyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fyv 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/fy/2fyv_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=2fyv ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The synthesis of two novel amino acids, nitrogen analogues of the naturally occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt are described, along with the crystal structure of one of these analogues in the active site of Drosophila melanogaster Golgi mannosidase II (dGMII). Salacinol, a naturally occurring sulfonium ion, is one of the active principals in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino l- or d-arabinitol at the least hindered carbon of 5,6-anhydro-2,3-di-O-benzyl-l-ascorbic acid to yield coupled adducts. Deprotection, stereoselective catalytic reduction, and hydrolysis of the coupled products give the target compounds. The compound derived from d-arabinitol inhibits dGMII, one of the critical enzymes in the glycoprotein processing pathway, with an IC(50) of 0.3mM. Inhibition of GMII has been identified as a target for control of metastatic cancer. An X-ray crystal structure of the complex of this compound with dGMII provides insight into the requirements for an effective inhibitor. The same compound inhibits recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with a K(i) value of 21microM. |
| | | | |
| - | '''Golgi alpha-mannosidase II complex with an amino-salacinol carboxylate analog'''
| + | Synthesis, enzymatic activity, and X-ray crystallography of an unusual class of amino acids.,Chen W, Kuntz DA, Hamlet T, Sim L, Rose DR, Mario Pinto B Bioorg Med Chem. 2006 Dec 15;14(24):8332-40. Epub 2006 Sep 28. PMID:17010621<ref>PMID:17010621</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2fyv" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | The synthesis of two novel amino acids, nitrogen analogues of the naturally occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt are described, along with the crystal structure of one of these analogues in the active site of Drosophila melanogaster Golgi mannosidase II (dGMII). Salacinol, a naturally occurring sulfonium ion, is one of the active principals in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino l- or d-arabinitol at the least hindered carbon of 5,6-anhydro-2,3-di-O-benzyl-l-ascorbic acid to yield coupled adducts. Deprotection, stereoselective catalytic reduction, and hydrolysis of the coupled products give the target compounds. The compound derived from d-arabinitol inhibits dGMII, one of the critical enzymes in the glycoprotein processing pathway, with an IC(50) of 0.3mM. Inhibition of GMII has been identified as a target for control of metastatic cancer. An X-ray crystal structure of the complex of this compound with dGMII provides insight into the requirements for an effective inhibitor. The same compound inhibits recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with a K(i) value of 21microM.
| + | *[[Mannosidase 3D structures|Mannosidase 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 2FYV 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=2FYV OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | Synthesis, enzymatic activity, and X-ray crystallography of an unusual class of amino acids., Chen W, Kuntz DA, Hamlet T, Sim L, Rose DR, Mario Pinto B, Bioorg Med Chem. 2006 Dec 15;14(24):8332-40. Epub 2006 Sep 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17010621 17010621]
| + | |
| | [[Category: Drosophila melanogaster]] | | [[Category: Drosophila melanogaster]] |
| - | [[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Single protein]]
| + | [[Category: Hamlet T]] |
| - | [[Category: Hamlet, T.]] | + | [[Category: Kuntz DA]] |
| - | [[Category: Kuntz, D A]] | + | [[Category: Rose DR]] |
| - | [[Category: Rose, D R.]] | + | |
| - | [[Category: MPD]]
| + | |
| - | [[Category: NAG]]
| + | |
| - | [[Category: PO4]]
| + | |
| - | [[Category: W72]]
| + | |
| - | [[Category: ZN]]
| + | |
| - | [[Category: glycosyl hydrolase family 38]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:58:27 2008''
| + | |
| Structural highlights
2fyv is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.9Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The synthesis of two novel amino acids, nitrogen analogues of the naturally occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt are described, along with the crystal structure of one of these analogues in the active site of Drosophila melanogaster Golgi mannosidase II (dGMII). Salacinol, a naturally occurring sulfonium ion, is one of the active principals in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino l- or d-arabinitol at the least hindered carbon of 5,6-anhydro-2,3-di-O-benzyl-l-ascorbic acid to yield coupled adducts. Deprotection, stereoselective catalytic reduction, and hydrolysis of the coupled products give the target compounds. The compound derived from d-arabinitol inhibits dGMII, one of the critical enzymes in the glycoprotein processing pathway, with an IC(50) of 0.3mM. Inhibition of GMII has been identified as a target for control of metastatic cancer. An X-ray crystal structure of the complex of this compound with dGMII provides insight into the requirements for an effective inhibitor. The same compound inhibits recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with a K(i) value of 21microM.
Synthesis, enzymatic activity, and X-ray crystallography of an unusual class of amino acids.,Chen W, Kuntz DA, Hamlet T, Sim L, Rose DR, Mario Pinto B Bioorg Med Chem. 2006 Dec 15;14(24):8332-40. Epub 2006 Sep 28. PMID:17010621[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen W, Kuntz DA, Hamlet T, Sim L, Rose DR, Mario Pinto B. Synthesis, enzymatic activity, and X-ray crystallography of an unusual class of amino acids. Bioorg Med Chem. 2006 Dec 15;14(24):8332-40. Epub 2006 Sep 28. PMID:17010621 doi:10.1016/j.bmc.2006.09.004
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