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| | ==Three tetrameric rings of Isoaspartyl Dipeptidase fitted in an EM volume.== | | ==Three tetrameric rings of Isoaspartyl Dipeptidase fitted in an EM volume.== |
| - | <StructureSection load='5lp3' size='340' side='right' caption='[[5lp3]], [[Resolution|resolution]] 10.50Å' scene=''> | + | <SX load='5lp3' size='340' side='right' viewer='molstar' caption='[[5lp3]], [[Resolution|resolution]] 10.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lp3]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LP3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LP3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lp3]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LP3 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 10.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">iadA, yjiF, b4328, JW4291 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></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=5lp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lp3 OCA], [http://pdbe.org/5lp3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lp3 RCSB], [http://www.ebi.ac.uk/pdbsum/5lp3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lp3 ProSAT]</span></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=5lp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lp3 OCA], [https://pdbe.org/5lp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lp3 RCSB], [https://www.ebi.ac.uk/pdbsum/5lp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lp3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IADA_ECOLI IADA_ECOLI]] Catalyzes the hydrolytic cleavage of a subset of L-isoaspartyl (L-beta-aspartyl) dipeptides. Used to degrade proteins damaged by L-isoaspartyl residues formation. The best substrate for the enzyme reported thus far is iso-Asp-Leu.<ref>PMID:7876157</ref> <ref>PMID:4880759</ref> <ref>PMID:12718528</ref> <ref>PMID:15882050</ref> | + | [https://www.uniprot.org/uniprot/IADA_ECOLI IADA_ECOLI] Catalyzes the hydrolytic cleavage of a subset of L-isoaspartyl (L-beta-aspartyl) dipeptides. Used to degrade proteins damaged by L-isoaspartyl residues formation. The best substrate for the enzyme reported thus far is iso-Asp-Leu.<ref>PMID:7876157</ref> <ref>PMID:4880759</ref> <ref>PMID:12718528</ref> <ref>PMID:15882050</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5lp3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5lp3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Isoaspartyl dipeptidase|Isoaspartyl dipeptidase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Elad, N]] | + | [[Category: Large Structures]] |
| - | [[Category: Empereur-Mot, C]] | + | [[Category: Elad N]] |
| - | [[Category: Garcia-Seisdedos, H]] | + | [[Category: Empereur-Mot C]] |
| - | [[Category: Levy, E D]] | + | [[Category: Garcia-Seisdedos H]] |
| - | [[Category: Designed protein filament]]
| + | [[Category: Levy ED]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Isoaspartyl dipeptidase]]
| + | |
| Structural highlights
Function
IADA_ECOLI Catalyzes the hydrolytic cleavage of a subset of L-isoaspartyl (L-beta-aspartyl) dipeptides. Used to degrade proteins damaged by L-isoaspartyl residues formation. The best substrate for the enzyme reported thus far is iso-Asp-Leu.[1] [2] [3] [4]
Publication Abstract from PubMed
The self-association of proteins into symmetric complexes is ubiquitous in all kingdoms of life. Symmetric complexes possess unique geometric and functional properties, but their internal symmetry can pose a risk. In sickle-cell disease, the symmetry of haemoglobin exacerbates the effect of a mutation, triggering assembly into harmful fibrils. Here we examine the universality of this mechanism and its relation to protein structure geometry. We introduced point mutations solely designed to increase surface hydrophobicity among 12 distinct symmetric complexes from Escherichia coli. Notably, all responded by forming supramolecular assemblies in vitro, as well as in vivo upon heterologous expression in Saccharomyces cerevisiae. Remarkably, in four cases, micrometre-long fibrils formed in vivo in response to a single point mutation. Biophysical measurements and electron microscopy revealed that mutants self-assembled in their folded states and so were not amyloid-like. Structural examination of 73 mutants identified supramolecular assembly hot spots predictable by geometry. A subsequent structural analysis of 7,471 symmetric complexes showed that geometric hot spots were buffered chemically by hydrophilic residues, suggesting a mechanism preventing mis-assembly of these regions. Thus, point mutations can frequently trigger folded proteins to self-assemble into higher-order structures. This potential is counterbalanced by negative selection and can be exploited to design nanomaterials in living cells.
Proteins evolve on the edge of supramolecular self-assembly.,Garcia-Seisdedos H, Empereur-Mot C, Elad N, Levy ED Nature. 2017 Aug 10;548(7666):244-247. doi: 10.1038/nature23320. Epub 2017 Aug 2. PMID:28783726[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gary JD, Clarke S. Purification and characterization of an isoaspartyl dipeptidase from Escherichia coli. J Biol Chem. 1995 Feb 24;270(8):4076-87. PMID:7876157
- ↑ Haley EE. Purification and properties of a beta-aspartyl peptidase from Escherichia coli. J Biol Chem. 1968 Nov 10;243(21):5748-52. PMID:4880759
- ↑ Thoden JB, Marti-Arbona R, Raushel FM, Holden HM. High-resolution X-ray structure of isoaspartyl dipeptidase from Escherichia coli. Biochemistry. 2003 May 6;42(17):4874-82. PMID:12718528 doi:http://dx.doi.org/10.1021/bi034233p
- ↑ Marti-Arbona R, Fresquet V, Thoden JB, Davis ML, Holden HM, Raushel FM. Mechanism of the reaction catalyzed by isoaspartyl dipeptidase from Escherichia coli. Biochemistry. 2005 May 17;44(19):7115-24. PMID:15882050 doi:10.1021/bi050008r
- ↑ Garcia-Seisdedos H, Empereur-Mot C, Elad N, Levy ED. Proteins evolve on the edge of supramolecular self-assembly. Nature. 2017 Aug 10;548(7666):244-247. doi: 10.1038/nature23320. Epub 2017 Aug 2. PMID:28783726 doi:http://dx.doi.org/10.1038/nature23320
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