7mk4: Difference between revisions
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==Co-bound crystal structure of the engineered cyt cb562 variant, DiCyt2== | ==Co-bound crystal structure of the engineered cyt cb562 variant, DiCyt2== | ||
<StructureSection load='7mk4' size='340' side='right'caption='[[7mk4]]' scene=''> | <StructureSection load='7mk4' size='340' side='right'caption='[[7mk4]], [[Resolution|resolution]] 1.27Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MK4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7mk4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MK4 FirstGlance]. <br> | ||
</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=7mk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mk4 OCA], [https://pdbe.org/7mk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mk4 RCSB], [https://www.ebi.ac.uk/pdbsum/7mk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mk4 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=O:OXYGEN+ATOM'>O</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=7mk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mk4 OCA], [https://pdbe.org/7mk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mk4 RCSB], [https://www.ebi.ac.uk/pdbsum/7mk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mk4 ProSAT]</span></td></tr> | |||
</table> | </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 coordination is central to the functions of metalloproteins:(1,2) each metalloprotein must pair with its cognate metallocofactor to fulfil its biological role(3). However, achieving metal selectivity solely through a three-dimensional protein structure is a great challenge, because there is a limited set of metal-coordinating amino acid functionalities and proteins are inherently flexible, which impedes steric selection of metals(3,4). Metal-binding affinities of natural proteins are primarily dictated by the electronic properties of metal ions and follow the Irving-Williams series(5) (Mn(2+) < Fe(2+) < Co(2+) < Ni(2+) < Cu(2+) > Zn(2+)) with few exceptions(6,7). Accordingly, metalloproteins overwhelmingly bind Cu(2+) and Zn(2+) in isolation, regardless of the nature of their active sites and their cognate metal ions(1,3,8). This led organisms to evolve complex homeostatic machinery and non-equilibrium strategies to achieve correct metal speciation(1,3,8-10). Here we report an artificial dimeric protein, (AB)2, that thermodynamically overcomes the Irving-Williams restrictions in vitro and in cells, favouring the binding of lower-Irving-Williams transition metals over Cu(2+), the most dominant ion in the Irving-Williams series. Counter to the convention in molecular design of achieving specificity through structural preorganization, (AB)2 was deliberately designed to be flexible. This flexibility enabled (AB)2 to adopt mutually exclusive, metal-dependent conformational states, which led to the discovery of structurally coupled coordination sites that disfavour Cu(2+) ions by enforcing an unfavourable coordination geometry. Aside from highlighting flexibility as a valuable element in protein design, our results illustrate design principles for constructing selective metal sequestration agents. | |||
Overcoming universal restrictions on metal selectivity by protein design.,Choi TS, Tezcan FA Nature. 2022 Mar;603(7901):522-527. doi: 10.1038/s41586-022-04469-8. Epub 2022, Mar 2. PMID:35236987<ref>PMID:35236987</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7mk4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Choi | [[Category: Choi, T S]] | ||
[[Category: Tezcan | [[Category: Tezcan, F A]] | ||
[[Category: Irving-williams series]] | |||
[[Category: Metal binding protein]] | |||
[[Category: Metal selectivity]] | |||
Revision as of 10:32, 29 June 2022
Co-bound crystal structure of the engineered cyt cb562 variant, DiCyt2Co-bound crystal structure of the engineered cyt cb562 variant, DiCyt2
Structural highlights
Function[C562_ECOLX] Electron-transport protein of unknown function. Publication Abstract from PubMedSelective metal coordination is central to the functions of metalloproteins:(1,2) each metalloprotein must pair with its cognate metallocofactor to fulfil its biological role(3). However, achieving metal selectivity solely through a three-dimensional protein structure is a great challenge, because there is a limited set of metal-coordinating amino acid functionalities and proteins are inherently flexible, which impedes steric selection of metals(3,4). Metal-binding affinities of natural proteins are primarily dictated by the electronic properties of metal ions and follow the Irving-Williams series(5) (Mn(2+) < Fe(2+) < Co(2+) < Ni(2+) < Cu(2+) > Zn(2+)) with few exceptions(6,7). Accordingly, metalloproteins overwhelmingly bind Cu(2+) and Zn(2+) in isolation, regardless of the nature of their active sites and their cognate metal ions(1,3,8). This led organisms to evolve complex homeostatic machinery and non-equilibrium strategies to achieve correct metal speciation(1,3,8-10). Here we report an artificial dimeric protein, (AB)2, that thermodynamically overcomes the Irving-Williams restrictions in vitro and in cells, favouring the binding of lower-Irving-Williams transition metals over Cu(2+), the most dominant ion in the Irving-Williams series. Counter to the convention in molecular design of achieving specificity through structural preorganization, (AB)2 was deliberately designed to be flexible. This flexibility enabled (AB)2 to adopt mutually exclusive, metal-dependent conformational states, which led to the discovery of structurally coupled coordination sites that disfavour Cu(2+) ions by enforcing an unfavourable coordination geometry. Aside from highlighting flexibility as a valuable element in protein design, our results illustrate design principles for constructing selective metal sequestration agents. Overcoming universal restrictions on metal selectivity by protein design.,Choi TS, Tezcan FA Nature. 2022 Mar;603(7901):522-527. doi: 10.1038/s41586-022-04469-8. Epub 2022, Mar 2. PMID:35236987[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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