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| | <StructureSection load='2aqv' size='340' side='right'caption='[[2aqv]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='2aqv' size='340' side='right'caption='[[2aqv]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2aqv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AQV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2aqv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AQV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.95Å</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> | + | <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>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2aqo|2aqo]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">iadA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=2aqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aqv OCA], [https://pdbe.org/2aqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aqv RCSB], [https://www.ebi.ac.uk/pdbsum/2aqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aqv 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=2aqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aqv OCA], [https://pdbe.org/2aqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aqv RCSB], [https://www.ebi.ac.uk/pdbsum/2aqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aqv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Holden, H M]] | + | [[Category: Holden HM]] |
| - | [[Category: Marti-Arbona, R]] | + | [[Category: Marti-Arbona R]] |
| - | [[Category: Raushel, F M]] | + | [[Category: Raushel FM]] |
| - | [[Category: Thoden, J B]] | + | [[Category: Thoden JB]] |
| - | [[Category: Dipeptidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metallo-protease]]
| + | |
| 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]
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
Isoaspartyl dipeptidase (IAD) is a binuclear metalloenzyme and a member of the amidohydrolase superfamily. This enzyme catalyzes the hydrolytic cleavage of beta-aspartyl dipeptides. The pH-rate profiles for the hydrolysis of beta-Asp-Leu indicates that catalysis is dependent on the ionization of two groups; one that ionizes at a pH approximately 6 and the other approximately 9. The group that must be ionized for catalysis is directly dependent on the identity of the metal ion bound to the active site. This result is consistent with the ionization of the hydroxide that bridges the two divalent cations. In addition to the residues that interact directly with the divalent cations there are two other residues that are highly conserved and found within the active site: Glu-77 and Tyr-137. Mutation of Tyr-137 to phenylalanine reduced the rate of catalysis by three orders of magnitude. The three dimensional X-ray structure of the Y137F mutant did not show any significant conformation changes relative to the three dimensional structure of the wild-type enzyme. The positioning of the side-chain phenolic group of Tyr-137 in the active site of IAD is consistent with the stabilization of the tetrahedral adduct concomitant with nucleophilic attack by the hydroxide that bridges the two divalent cations. Mutation of Glu-77 resulted in the reduction of catalytic activity by five orders of magnitude. The three dimensional structure of the E77Q mutant did not show any significant conformational changes in the mutant relative to the three dimensional structure of the wild-type enzyme. The positioning of the side-chain carboxylate of Glu-77 is consistent with the formation of an ion pair interaction with the free alpha-amino group of the substrate.
Functional significance of Glu-77 and Tyr-137 within the active site of isoaspartyl dipeptidase.,Marti-Arbona R, Thoden JB, Holden HM, Raushel FM Bioorg Chem. 2005 Dec;33(6):448-58. Epub 2005 Nov 11. PMID:16289685[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
- ↑ Marti-Arbona R, Thoden JB, Holden HM, Raushel FM. Functional significance of Glu-77 and Tyr-137 within the active site of isoaspartyl dipeptidase. Bioorg Chem. 2005 Dec;33(6):448-58. Epub 2005 Nov 11. PMID:16289685 doi:10.1016/j.bioorg.2005.10.002
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