8drd - Revision history

OCA at 12:03, 23 October 2024

2024-10-23T12:03:24Z

← Older revision		Revision as of 12:03, 23 October 2024
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	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	Selective metal binding is a key requirement not only for the functions of natural metalloproteins but also for the potential applications of artificial metalloproteins in heterogeneous environments such as cells and environmental samples. The selection of transition-metal ions through protein design can, in principle, be achieved through the appropriate choice and the precise positioning of amino acids that comprise the primary metal coordination sphere. However, this task is made difficult by the intrinsic flexibility of proteins and the fact that protein design approaches generally lack the sub-A precision required for the steric selection of metal ions. We recently introduced a flexible/probabilistic protein design strategy (MASCoT) that allows metal ions to search for optimal coordination geometry within a flexible, yet covalently constrained dimer interface. In an earlier proof-of-principle study, we used MASCoT to generate an artificial metalloprotein dimer, (AB)2, which selectively bound Co(II) and Ni(II) over Cu(II) (as well as other first-row transition-metal ions) through the imposition of a rigid octahedral coordination geometry, thus countering the Irving-Williams trend. In this study, we set out to redesign (AB)2 to examine the applicability of MASCoT to the selective binding of other metal ions. We report here the design and characterization of a new flexible protein dimer, B2, which displays Zn(II) selectivity over all other tested metal ions including Cu(II) both in vitro and in cellulo. Selective, anti-Irving-Williams Zn(II) binding by B2 is achieved through the formation of a unique trinuclear Zn coordination motif in which His and Glu residues are rigidly placed in a tetrahedral geometry. These results highlight the utility of protein flexibility in the design and discovery of selective binding motifs.		Selective metal binding is a key requirement not only for the functions of natural metalloproteins but also for the potential applications of artificial metalloproteins in heterogeneous environments such as cells and environmental samples. The selection of transition-metal ions through protein design can, in principle, be achieved through the appropriate choice and the precise positioning of amino acids that comprise the primary metal coordination sphere. However, this task is made difficult by the intrinsic flexibility of proteins and the fact that protein design approaches generally lack the sub-A precision required for the steric selection of metal ions. We recently introduced a flexible/probabilistic protein design strategy (MASCoT) that allows metal ions to search for optimal coordination geometry within a flexible, yet covalently constrained dimer interface. In an earlier proof-of-principle study, we used MASCoT to generate an artificial metalloprotein dimer, (AB)(2), which selectively bound Co(II) and Ni(II) over Cu(II) (as well as other first-row transition-metal ions) through the imposition of a rigid octahedral coordination geometry, thus countering the Irving-Williams trend. In this study, we set out to redesign (AB)(2) to examine the applicability of MASCoT to the selective binding of other metal ions. We report here the design and characterization of a new flexible protein dimer, B(2), which displays Zn(II) selectivity over all other tested metal ions including Cu(II) both in vitro and in cellulo. Selective, anti-Irving-Williams Zn(II) binding by B(2) is achieved through the formation of a unique trinuclear Zn coordination motif in which His and Glu residues are rigidly placed in a tetrahedral geometry. These results highlight the utility of protein flexibility in the design and discovery of selective binding motifs.

	Design of a Flexible, Zn-Selective Protein Scaffold that Displays Anti-Irving-Williams Behavior.,Choi TS, Tezcan FA J Am Chem Soc. 2022 Oct 5;144(39):18090-18100. doi: 10.1021/jacs.2c08050. Epub, 2022 Sep 26. PMID:36154053<ref>PMID:36154053</ref>		Design of a Flexible, Zn-Selective Protein Scaffold that Displays Anti-Irving-Williams Behavior.,Choi TS, Tezcan FA J Am Chem Soc. 2022 Oct 5;144(39):18090-18100. doi: 10.1021/jacs.2c08050. Epub , 2022 Sep 26. PMID:36154053<ref>PMID:36154053</ref>

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

OCA at 17:30, 18 October 2023

2023-10-18T17:30:14Z

← Older revision		Revision as of 17:30, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8drd]] 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=8DRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DRD FirstGlance]. <br>		<table><tr><td colspan='2'>[[8drd]] 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=8DRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DRD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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]] 1.89Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></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=8drd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8drd OCA], [https://pdbe.org/8drd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8drd RCSB], [https://www.ebi.ac.uk/pdbsum/8drd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8drd 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=8drd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8drd OCA], [https://pdbe.org/8drd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8drd RCSB], [https://www.ebi.ac.uk/pdbsum/8drd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8drd ProSAT]</span></td></tr>
	</table>		</table>

OCA at 19:36, 19 October 2022

2022-10-19T19:36:21Z

← Older revision		Revision as of 19:36, 19 October 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8drd is ~~ON HOLD until Paper~~ Publication		==Ni(II)-bound B2 dimer (H60/H100/H104)==
			<StructureSection load='8drd' size='340' side='right'caption='[[8drd]], [[Resolution\|resolution]] 1.89Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8drd]] 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=8DRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DRD FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></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=8drd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8drd OCA], [https://pdbe.org/8drd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8drd RCSB], [https://www.ebi.ac.uk/pdbsum/8drd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8drd ProSAT]</span></td></tr>
			</table>
			== Function ==
			[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Selective metal binding is a key requirement not only for the functions of natural metalloproteins but also for the potential applications of artificial metalloproteins in heterogeneous environments such as cells and environmental samples. The selection of transition-metal ions through protein design can, in principle, be achieved through the appropriate choice and the precise positioning of amino acids that comprise the primary metal coordination sphere. However, this task is made difficult by the intrinsic flexibility of proteins and the fact that protein design approaches generally lack the sub-A precision required for the steric selection of metal ions. We recently introduced a flexible/probabilistic protein design strategy (MASCoT) that allows metal ions to search for optimal coordination geometry within a flexible, yet covalently constrained dimer interface. In an earlier proof-of-principle study, we used MASCoT to generate an artificial metalloprotein dimer, (AB)2, which selectively bound Co(II) and Ni(II) over Cu(II) (as well as other first-row transition-metal ions) through the imposition of a rigid octahedral coordination geometry, thus countering the Irving-Williams trend. In this study, we set out to redesign (AB)2 to examine the applicability of MASCoT to the selective binding of other metal ions. We report here the design and characterization of a new flexible protein dimer, B2, which displays Zn(II) selectivity over all other tested metal ions including Cu(II) both in vitro and in cellulo. Selective, anti-Irving-Williams Zn(II) binding by B2 is achieved through the formation of a unique trinuclear Zn coordination motif in which His and Glu residues are rigidly placed in a tetrahedral geometry. These results highlight the utility of protein flexibility in the design and discovery of selective binding motifs.

	~~Authors:~~ Choi, T.S., ~~Tezcan, F.A~~.		Design of a Flexible, Zn-Selective Protein Scaffold that Displays Anti-Irving-Williams Behavior.,Choi TS, Tezcan FA J Am Chem Soc. 2022 Oct 5;144(39):18090-18100. doi: 10.1021/jacs.2c08050. Epub, 2022 Sep 26. PMID:36154053<ref>PMID:36154053</ref>

	~~Description~~: ~~Ni(II)-bound B2 dimer (H60~~/~~H100~~/~~H104)~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased~~ Structures]]		</div>
	[[Category: ~~Tezcan, F.A~~]]		<div class="pdbe-citations 8drd" style="background-color:#fffaf0;"></div>
	[[Category: ~~Choi, T.S~~]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Escherichia coli]]
			[[Category: Large Structures]]
			[[Category: Choi TS]]
			[[Category: Tezcan FA]]

OCA at 03:54, 3 August 2022

2022-08-03T03:54:26Z

← Older revision		Revision as of 03:54, 3 August 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8drd is ON HOLD		The entry 8drd is ON HOLD until Paper Publication

	Authors: Choi, T.S., Tezcan, F.A.		Authors: Choi, T.S., Tezcan, F.A.

OCA: Protected "8drd" [edit=sysop:move=sysop]

2022-07-27T16:48:07Z

Protected "8drd" [edit=sysop:move=sysop]

← Older revision	Revision as of 16:48, 27 July 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8drd is ON HOLD Authors: Choi, T.S., Tezcan, F.A. Description: Ni(II)-bound B2 dimer (H60/H100/H104) Category: Unreleased Structures [[Category...

2022-07-27T16:48:06Z

New page: '''Unreleased structure''' The entry 8drd is ON HOLD Authors: Choi, T.S., Tezcan, F.A. Description: Ni(II)-bound B2 dimer (H60/H100/H104) Category: Unreleased Structures [[Category...

New page

'''Unreleased structure'''

The entry 8drd is ON HOLD

Authors: Choi, T.S., Tezcan, F.A.

Description: Ni(II)-bound B2 dimer (H60/H100/H104)
[[Category: Unreleased Structures]]
[[Category: Tezcan, F.A]]
[[Category: Choi, T.S]]