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| | ==Crystal structure of insulysin with bound ATP== | | ==Crystal structure of insulysin with bound ATP== |
| - | <StructureSection load='3tuv' size='340' side='right' caption='[[3tuv]], [[Resolution|resolution]] 2.27Å' scene=''> | + | <StructureSection load='3tuv' size='340' side='right'caption='[[3tuv]], [[Resolution|resolution]] 2.27Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tuv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TUV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TUV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tuv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TUV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TUV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.27Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ide ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3tuv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tuv OCA], [https://pdbe.org/3tuv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tuv RCSB], [https://www.ebi.ac.uk/pdbsum/3tuv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tuv ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span></td></tr>
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| - | <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=3tuv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tuv OCA], [http://pdbe.org/3tuv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tuv RCSB], [http://www.ebi.ac.uk/pdbsum/3tuv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tuv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IDE_RAT IDE_RAT]] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. | + | [https://www.uniprot.org/uniprot/IDE_RAT IDE_RAT] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Insulin-degrading enzyme (IDE) (insulysin) is a zinc metallopeptidase that metabolizes several bioactive peptides, including insulin and the amyloid beta peptide. IDE is an unusual metallopeptidase in that it is allosterically activated by both small peptides and anions, such as ATP. Here, we report that the ATP-binding site is located on a portion of the substrate binding chamber wall arising largely from domain 4 of the four-domain IDE. Two variants having residues in this site mutated, IDE(K898A,K899A,S901A) and IDE(R429S), both show greatly decreased activation by the polyphosphate anions ATP and PPP(i). IDE(K898A,K899A,S901A) is also deficient in activation by small peptides, suggesting a possible mechanistic link between the two types of allosteric activation. Sodium chloride at high concentrations can also activate IDE. There are no observable differences in average conformation between the IDE-ATP complex and unliganded IDE, but regions of the active site and C-terminal domain do show increased crystallographic thermal factors in the complex, suggesting an effect on dynamics. Activation by ATP is shown to be independent of the ATP hydrolysis activity reported for the enzyme. We also report that IDE(K898A,K899A,S901A) has reduced intracellular function relative to unmodified IDE, consistent with a possible role for anion activation of IDE activity in vivo. Together, the data suggest a model in which the binding of anions activates by reducing the electrostatic attraction between the two halves of the enzyme, shifting the partitioning between open and closed conformations of IDE toward the open form.
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| - | Anion Activation Site of Insulin-degrading Enzyme.,Noinaj N, Song ES, Bhasin S, Alper BJ, Schmidt WK, Hersh LB, Rodgers DW J Biol Chem. 2012 Jan 2;287(1):48-57. Epub 2011 Nov 2. PMID:22049080<ref>PMID:22049080</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3tuv" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Insulin-Degrading Enzyme|Insulin-Degrading Enzyme]] | + | *[[Insulin-degrading enzyme 3D structures|Insulin-degrading enzyme 3D structures]] |
| - | *[[RNA polymerase|RNA polymerase]] | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Insulysin]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Noinaj, N]] | + | [[Category: Noinaj N]] |
| - | [[Category: Rodgers, D W]] | + | [[Category: Rodgers DW]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Hydrolyase]]
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| - | [[Category: Peptidase]]
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| - | [[Category: Thermolysin-like fold active site region]]
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