OCA at 05:58, 24 October 2018

OCA — Wed, 24 Oct 2018 05:58:01 GMT

←Older revision		Revision as of 05:58, 24 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6gbk is ~~ON HOLD until Paper~~ Publication	+	==Repertoires of functionally diverse enzymes through computational design at epistatic active-site positions==
		+	<StructureSection load='6gbk' size='340' side='right' caption='[[6gbk]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6gbk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GBK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GBK FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aryldialkylphosphatase Aryldialkylphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.8.1 3.1.8.1] </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=6gbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gbk OCA], [http://pdbe.org/6gbk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gbk RCSB], [http://www.ebi.ac.uk/pdbsum/6gbk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gbk ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/OPD_BREDI OPD_BREDI]] Has an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates. All of the phosphate triesters found to be substrates are synthetic compounds. The identity of any naturally occurring substrate for the enzyme is unknown. Has no detectable activity with phosphate monoesters or diesters and no activity as an esterase or protease. It catalyzes the hydrolysis of the insecticide paraoxon at a rate approaching the diffusion limit and thus appears to be optimally evolved for utilizing this synthetic substrate.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Substantial improvements in enzyme activity demand multiple mutations at spatially proximal positions in the active site. Such mutations, however, often exhibit unpredictable epistatic (non-additive) effects on activity. Here we describe FuncLib, an automated method for designing multipoint mutations at enzyme active sites using phylogenetic analysis and Rosetta design calculations. We applied FuncLib to two unrelated enzymes, a phosphotriesterase and an acetyl-CoA synthetase. All designs were active, and most showed activity profiles that significantly differed from the wild-type and from one another. Several dozen designs with only 3-6 active-site mutations exhibited 10- to 4,000-fold higher efficiencies with a range of alternative substrates, including hydrolysis of the toxic organophosphate nerve agents soman and cyclosarin and synthesis of butyryl-CoA. FuncLib is implemented as a web server (http://FuncLib.weizmann.ac.il); it circumvents iterative, high-throughput experimental screens and opens the way to designing highly efficient and diverse catalytic repertoires.

-	~~Authors:~~ Khersonsky, O., Lipsh, R., Avizemer, Z., Goldsmith, M~~., Ashani, Y.~~, Leader, H., Dym, O., Rogotner, S., Trudeau, D., Tawfik, D.S., ~~Fleishman, S.J~~.	+	Automated Design of Efficient and Functionally Diverse Enzyme Repertoires.,Khersonsky O, Lipsh R, Avizemer Z, Ashani Y, Goldsmith M, Leader H, Dym O, Rogotner S, Trudeau DL, Prilusky J, Amengual-Rigo P, Guallar V, Tawfik DS, Fleishman SJ Mol Cell. 2018 Oct 4;72(1):178-186.e5. doi: 10.1016/j.molcel.2018.08.033. Epub, 2018 Sep 27. PMID:30270109<ref>PMID:30270109</ref>

-	~~Description: Repertoires~~ of ~~functionally diverse enzymes through computational design at epistatic active~~-~~site positions~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Leader~~, H]]	+	<div class="pdbe-citations 6gbk" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Tawfik~~, D.S]]	+
		+	==See Also==
		+	*[[Journal:Molecular Cell:2\|Journal:Molecular Cell:2]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Aryldialkylphosphatase]]
		+	[[Category: Ashani, Y]]
		+	[[Category: Avizemer, Z]]
		+	[[Category: Dym, O]]
		+	[[Category: Fleishman, S J]]
	[[Category: Goldsmith, M]]		[[Category: Goldsmith, M]]
		+	[[Category: Khersonsky, O]]
		+	[[Category: Leader, H]]
	[[Category: Lipsh, R]]		[[Category: Lipsh, R]]
-	[[Category: Fleishman, S.J]]
-	[[Category: Avizemer, Z]]
	[[Category: Rogotner, S]]		[[Category: Rogotner, S]]
-	[[Category: ~~Ashani~~, ~~Y]]~~	+	[[Category: Tawfik, D S]]
-	~~[[Category: Dym, O~~]]	+
	[[Category: Trudeau, D]]		[[Category: Trudeau, D]]
-	[[Category: ~~Khersonsky, O~~]]	+	[[Category: Hydrolase]]
		+	[[Category: Phosphotriesterase]]

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

OCA — Wed, 25 Apr 2018 04:19:29 GMT

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

←Older revision

Revision as of 04:19, 25 April 2018

OCA: New page: '''Unreleased structure''' The entry 6gbk is ON HOLD until Paper Publication Authors: Khersonsky, O., Lipsh, R., Avizemer, Z., Goldsmith, M., Ashani, Y., Leader, H., Dym, O., Rogotner, ...

OCA — Wed, 25 Apr 2018 04:19:28 GMT

New page: '''Unreleased structure''' The entry 6gbk is ON HOLD until Paper Publication Authors: Khersonsky, O., Lipsh, R., Avizemer, Z., Goldsmith, M., Ashani, Y., Leader, H., Dym, O., Rogotner, ...

New page

'''Unreleased structure'''

The entry 6gbk is ON HOLD until Paper Publication

Authors: Khersonsky, O., Lipsh, R., Avizemer, Z., Goldsmith, M., Ashani, Y., Leader, H., Dym, O., Rogotner, S., Trudeau, D., Tawfik, D.S., Fleishman, S.J.

Description: Repertoires of functionally diverse enzymes through computational design at epistatic active-site positions
[[Category: Unreleased Structures]]
[[Category: Leader, H]]
[[Category: Tawfik, D.S]]
[[Category: Goldsmith, M]]
[[Category: Lipsh, R]]
[[Category: Fleishman, S.J]]
[[Category: Avizemer, Z]]
[[Category: Rogotner, S]]
[[Category: Ashani, Y]]
[[Category: Dym, O]]
[[Category: Trudeau, D]]
[[Category: Khersonsky, O]]

6gbk - Revision history

OCA at 05:58, 24 October 2018

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

OCA: New page: '''Unreleased structure''' The entry 6gbk is ON HOLD until Paper Publication Authors: Khersonsky, O., Lipsh, R., Avizemer, Z., Goldsmith, M., Ashani, Y., Leader, H., Dym, O., Rogotner, ...