6gmu - Revision history

OCA at 07:14, 8 April 2020

OCA — Wed, 08 Apr 2020 07:14:03 GMT

←Older revision		Revision as of 07:14, 8 April 2020
Line 3:		Line 3:
	<StructureSection load='6gmu' size='340' side='right'caption='[[6gmu]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='6gmu' size='340' side='right'caption='[[6gmu]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gmu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GMU OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6GMU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gmu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GMU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6GMU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6gmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gmu OCA], [http://pdbe.org/6gmu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gmu RCSB], [http://www.ebi.ac.uk/pdbsum/6gmu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gmu ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6gmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gmu OCA], [http://pdbe.org/6gmu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gmu RCSB], [http://www.ebi.ac.uk/pdbsum/6gmu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gmu ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	</div>		</div>
	<div class="pdbe-citations 6gmu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6gmu" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serum Paraoxonase\|Serum Paraoxonase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:57, 5 February 2020

OCA — Wed, 05 Feb 2020 08:57:59 GMT

←Older revision		Revision as of 08:57, 5 February 2020
Line 3:		Line 3:
	<StructureSection load='6gmu' size='340' side='right'caption='[[6gmu]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='6gmu' size='340' side='right'caption='[[6gmu]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gmu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GMU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GMU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gmu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GMU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GMU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6gmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gmu OCA], [http://pdbe.org/6gmu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gmu RCSB], [http://www.ebi.ac.uk/pdbsum/6gmu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gmu ProSAT]</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=6gmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gmu OCA], [http://pdbe.org/6gmu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gmu RCSB], [http://www.ebi.ac.uk/pdbsum/6gmu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gmu ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Evolutionary trajectories are deemed largely irreversible. In a newly diverged protein, reversion of mutations that led to the functional switch typically results in loss of both the new and ancestral functions. Nonetheless, evolutionary transitions where reversions are viable have also been described. The structural and mechanistic causes of reversion compatibility versus incompatibility therefore remain unclear. We examined two laboratory evolution trajectories of mammalian paraoxonase-1 (PON1), a lactonase with promiscuous organophosphate hydrolase (OPH) activity. Both trajectories began with the same active-site mutant, His115Trp, which lost the native lactonase activity and acquired higher OPH activity. A neo-functionalization trajectory amplified the promiscuous OPH activity, while the re-functionalization trajectory restored the native activity, thus generating a new lactonase that lacks His115. The His115 revertants of these trajectories indicated opposite trends. Revertants of the neo-functionalization trajectory lost both the evolved OPH and the original lactonase activity. Revertants of the trajectory that restored the original lactonase function were, however, fully active. Crystal structures and molecular simulations show that in the newly diverged OPH, the reverted His115 and other catalytic residues are displaced, thus causing loss of both the original and new activity. In contrast, in the re-functionalization trajectory, reversion compatibility of the original lactonase activity derives from mechanistic versatility whereby multiple residues can fulfill the same task. This versatility enables unique sequence-reversible compositions that are inaccessible when the active site was repurposed toward a new function.
		+
		+	Enzyme neo- versus re-functionalization - an epistatic ratchet versus a smooth reversible transition.,Ben-David M, Soskine M, Dubovetskyi A, Cherukuri KP, Dym O, Sussman JL, Liao Q, Szeler K, Kamerlin SCL, Tawfik DS Mol Biol Evol. 2019 Dec 24. pii: 5686393. doi: 10.1093/molbev/msz298. PMID:31873734<ref>PMID:31873734</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6gmu" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Ben-David, M]]		[[Category: Ben-David, M]]

OCA at 05:56, 17 April 2019

OCA — Wed, 17 Apr 2019 05:56:49 GMT

←Older revision		Revision as of 05:56, 17 April 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6gmu is ON HOLD~~	+	==Serum paraoxonase-1 by directed evolution with the L69G/H134R/F222S/T332S mutations==
-		+	<StructureSection load='6gmu' size='340' side='right'caption='[[6gmu]], [[Resolution\|resolution]] 2.70Å' scene=''>
-	~~Authors: Ben-David, M., Sussman, J.L., Tawfik, D.S.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6gmu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GMU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GMU FirstGlance]. <br>
-	~~Description:~~ Serum paraoxonase-1 by directed evolution with the L69G/H134R/F222S/T332S mutations	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=6gmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gmu OCA], [http://pdbe.org/6gmu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gmu RCSB], [http://www.ebi.ac.uk/pdbsum/6gmu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gmu ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Tawfik~~, D.S]]	+	</table>
-	[[~~Category~~: ~~Sussman~~, J.L]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Ben-David, M]]		[[Category: Ben-David, M]]
		+	[[Category: Sussman, J L]]
		+	[[Category: Tawfik, D S]]
		+	[[Category: Beta-propeller]]
		+	[[Category: Hdl]]
		+	[[Category: Hydrolase]]
		+	[[Category: Lactonase]]
		+	[[Category: Organophosphate-hydrolase]]

OCA: Protected "6gmu" [edit=sysop:move=sysop]

OCA — Wed, 06 Jun 2018 04:29:48 GMT

Protected "6gmu" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:29, 6 June 2018

OCA: New page: '''Unreleased structure''' The entry 6gmu is ON HOLD Authors: Ben-David, M., Sussman, J.L., Tawfik, D.S. Description: Serum paraoxonase-1 by directed evolution with the L69G/H134R/F222...

OCA — Wed, 06 Jun 2018 04:29:47 GMT

New page: '''Unreleased structure''' The entry 6gmu is ON HOLD Authors: Ben-David, M., Sussman, J.L., Tawfik, D.S. Description: Serum paraoxonase-1 by directed evolution with the L69G/H134R/F222...

New page

'''Unreleased structure'''

The entry 6gmu is ON HOLD

Authors: Ben-David, M., Sussman, J.L., Tawfik, D.S.

Description: Serum paraoxonase-1 by directed evolution with the L69G/H134R/F222S/T332S mutations
[[Category: Unreleased Structures]]
[[Category: Tawfik, D.S]]
[[Category: Sussman, J.L]]
[[Category: Ben-David, M]]