4ypm: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 4ypm is ~~ON HOLD until Paper~~ Publication

==Crystal structure of a LonA protease domain in complex with bortezomib==

== Structural highlights ==

<table><tr><td colspan='2'>[[4ypm]] is a 1 chain structure. 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>

</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>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ypl|4ypl]], [[4ypn|4ypn]]</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]</span></td></tr>

</table>

== 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]

== 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.

~~Authors:~~ Lin, ~~C.-C.~~, Chang, C.-I.

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<ref>PMID:27041593</ref>

~~Description~~: ~~Crystal structure of a LonA protease domain in complex with bortezomib~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased Structures~~]]

</div>

[[Category: Lin, C.-C]]

[[Category: ~~Chang, C.-I~~]]

== References ==

__TOC__

</StructureSection>

[[Category: Endopeptidase La]]

[[Category: Chang, C I]]

[[Category: Lin, C C]]

[[Category: Aaa+ domain]]

[[Category: Bortezomib]]

[[Category: Hydrolase]]

[[Category: Lon protease]]

[[Category: Magnesium]]

[[Category: Protease domain]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4ypm is ON HOLD  until Paper Publication
+==Crystal structure of a LonA protease domain in complex with bortezomib==
+<StructureSection load='4ypm' size='340' side='right' caption='[[4ypm]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ypm]] is a 1 chain structure. 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>
+</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>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ypl|4ypl]], [[4ypn|4ypn]]</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]</span></td></tr>
+</table>
+== 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]
+<div style="background-color:#fffaf0;">
+== 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.
-Authors: Lin, C.-C., Chang, C.-I.
+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<ref>PMID:27041593</ref>
-Description: Crystal structure of a LonA protease domain in complex with bortezomib
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Lin, C.-C]]
+<div class="pdbe-citations 4ypm" style="background-color:#fffaf0;"></div>
-[[Category: Chang, C.-I]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Endopeptidase La]]
+[[Category: Chang, C I]]
+[[Category: Lin, C C]]
+[[Category: Aaa+ domain]]
+[[Category: Bortezomib]]
+[[Category: Hydrolase]]
+[[Category: Lon protease]]
+[[Category: Magnesium]]
+[[Category: Protease domain]]