|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4w93' size='340' side='right'caption='[[4w93]], [[Resolution|resolution]] 1.35Å' scene=''> | | <StructureSection load='4w93' size='340' side='right'caption='[[4w93]], [[Resolution|resolution]] 1.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4w93]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4W93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4W93 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4w93]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4W93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4W93 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3L9:MONTBRETIN+A'>3L9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3L9:MONTBRETIN+A'>3L9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=4w93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w93 OCA], [https://pdbe.org/4w93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4w93 RCSB], [https://www.ebi.ac.uk/pdbsum/4w93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4w93 ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bsi|1bsi]], [[1hny|1hny]], [[1cpu|1cpu]], [[4gqr|4gqr]], [[4gqq|4gqq]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AMY2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alpha-amylase Alpha-amylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.1 3.2.1.1] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4w93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w93 OCA], [http://pdbe.org/4w93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4w93 RCSB], [http://www.ebi.ac.uk/pdbsum/4w93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4w93 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/AMYP_HUMAN AMYP_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alpha-amylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brayer, G D]] | + | [[Category: Brayer GD]] |
| - | [[Category: Caner, S]] | + | [[Category: Caner S]] |
| - | [[Category: Williams, L K]] | + | [[Category: Williams LK]] |
| - | [[Category: Amylase]]
| + | |
| - | [[Category: Diabetes]]
| + | |
| - | [[Category: Enzyme inhibitor]]
| + | |
| - | [[Category: Glucosyl hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
Function
AMYP_HUMAN
Publication Abstract from PubMed
The complex plant flavonol glycoside montbretin A is a potent (Ki = 8 nM) and specific inhibitor of human pancreatic alpha-amylase with potential as a therapeutic for diabetes and obesity. Controlled degradation studies on montbretin A, coupled with inhibition analyses, identified an essential high-affinity core structure comprising the myricetin and caffeic acid moieties linked via a disaccharide. X-ray structural analyses of the montbretin A-human alpha-amylase complex confirmed the importance of this core structure and revealed a novel mode of glycosidase inhibition wherein internal pi-stacking interactions between the myricetin and caffeic acid organize their ring hydroxyls for optimal hydrogen bonding to the alpha-amylase catalytic residues D197 and E233. This novel inhibitory motif can be reproduced in a greatly simplified analog, offering potential for new strategies for glycosidase inhibition and therapeutic development.
The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif.,Williams LK, Zhang X, Caner S, Tysoe C, Nguyen NT, Wicki J, Williams DE, Coleman J, McNeill JH, Yuen V, Andersen RJ, Withers SG, Brayer GD Nat Chem Biol. 2015 Jul 27. doi: 10.1038/nchembio.1865. PMID:26214255[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Williams LK, Zhang X, Caner S, Tysoe C, Nguyen NT, Wicki J, Williams DE, Coleman J, McNeill JH, Yuen V, Andersen RJ, Withers SG, Brayer GD. The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif. Nat Chem Biol. 2015 Jul 27. doi: 10.1038/nchembio.1865. PMID:26214255 doi:http://dx.doi.org/10.1038/nchembio.1865
|
