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| | ==Crystal structure of a LonA protease domain in complex with bortezomib== | | ==Crystal structure of a LonA protease domain in complex with bortezomib== |
| - | <StructureSection load='4ypm' size='340' side='right' caption='[[4ypm]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='4ypm' size='340' side='right'caption='[[4ypm]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ypm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_baa-399 Atcc baa-399]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YPM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ypm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Meiothermus_taiwanensis Meiothermus taiwanensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YPM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BO2:N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE'>BO2</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BO2:N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE'>BO2</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ypl|4ypl]], [[4ypn|4ypn]]</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=4ypm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypm OCA], [https://pdbe.org/4ypm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ypm RCSB], [https://www.ebi.ac.uk/pdbsum/4ypm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ypm ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lonA1, lon ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=172827 ATCC BAA-399])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endopeptidase_La Endopeptidase La], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.53 3.4.21.53] </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=4ypm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypm OCA], [http://pdbe.org/4ypm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ypm RCSB], [http://www.ebi.ac.uk/pdbsum/4ypm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ypm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A059VAZ3_9DEIN A0A059VAZ3_9DEIN]] ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins as well as certain short-lived regulatory proteins. Required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress. Degrades polypeptides processively to yield small peptide fragments that are 5 to 10 amino acids long. Binds to DNA in a double-stranded, site-specific manner.[HAMAP-Rule:MF_01973] | + | [https://www.uniprot.org/uniprot/A0A059VAZ3_9DEIN A0A059VAZ3_9DEIN] ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins as well as certain short-lived regulatory proteins. Required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress. Degrades polypeptides processively to yield small peptide fragments that are 5 to 10 amino acids long. Binds to DNA in a double-stranded, site-specific manner.[HAMAP-Rule:MF_01973] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc baa-399]] | + | [[Category: Large Structures]] |
| - | [[Category: Endopeptidase La]] | + | [[Category: Meiothermus taiwanensis]] |
| - | [[Category: Chang, C I]] | + | [[Category: Chang C-I]] |
| - | [[Category: Lin, C C]] | + | [[Category: Lin C-C]] |
| - | [[Category: Aaa+ domain]]
| + | |
| - | [[Category: Bortezomib]]
| + | |
| - | [[Category: Hydrolase]]
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| - | [[Category: Lon protease]]
| + | |
| - | [[Category: Magnesium]]
| + | |
| - | [[Category: Protease domain]]
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| Structural highlights
Function
A0A059VAZ3_9DEIN ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins as well as certain short-lived regulatory proteins. Required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress. Degrades polypeptides processively to yield small peptide fragments that are 5 to 10 amino acids long. Binds to DNA in a double-stranded, site-specific manner.[HAMAP-Rule:MF_01973]
Publication Abstract from PubMed
The Lon AAA+ protease (LonA) plays important roles in protein homeostasis and regulation of diverse biological processes. LonA behaves as a homomeric hexamer in the presence of magnesium (Mg(2+)) and performs ATP-dependent proteolysis. However, it is also found that LonA can carry out Mg(2+)-dependent degradation of unfolded protein substrate in an ATP-independent manner. Here we show that in the presence of Mg(2+) LonA forms a non-secluded hexameric barrel with prominent openings, which explains why Mg(2+)-activated LonA can operate as a diffusion-based chambered protease to degrade unstructured protein and peptide substrates efficiently in the absence of ATP. A 1.85 A crystal structure of Mg(2+)-activated protease domain reveals Mg(2+)-dependent remodeling of a substrate-binding loop and a potential metal-binding site near the Ser-Lys catalytic dyad, supported by biophysical binding assays and molecular dynamics simulations. Together, these findings reveal the specific roles of Mg(2+) in the molecular assembly and activation of LonA.
Structural Basis for the Magnesium-Dependent Activation and Hexamerization of the Lon AAA+ Protease.,Su SC, Lin CC, Tai HC, Chang MY, Ho MR, Babu CS, Liao JH, Wu SH, Chang YC, Lim C, Chang CI Structure. 2016 May 3;24(5):676-86. doi: 10.1016/j.str.2016.03.003. Epub 2016 Mar, 31. PMID:27041593[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Su SC, Lin CC, Tai HC, Chang MY, Ho MR, Babu CS, Liao JH, Wu SH, Chang YC, Lim C, Chang CI. Structural Basis for the Magnesium-Dependent Activation and Hexamerization of the Lon AAA+ Protease. Structure. 2016 May 3;24(5):676-86. doi: 10.1016/j.str.2016.03.003. Epub 2016 Mar, 31. PMID:27041593 doi:http://dx.doi.org/10.1016/j.str.2016.03.003
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