4hr0: Difference between revisions
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==R2-like ligand-binding oxidase with aerobically reconstituted metal cofactor== | |||
<StructureSection load='4hr0' size='340' side='right' caption='[[4hr0]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4hr0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Geobacillus_kaustophilus_hta426 Geobacillus kaustophilus hta426]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HR0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HR0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MN3:MANGANESE+(III)+ION'>MN3</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hr4|4hr4]], [[4hr5|4hr5]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GK2771 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=235909 Geobacillus kaustophilus HTA426])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] </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=4hr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hr0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hr0 RCSB], [http://www.ebi.ac.uk/pdbsum/4hr0 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Although metallocofactors are ubiquitous in enzyme catalysis, how metal binding specificity arises remains poorly understood, especially in the case of metals with similar primary ligand preferences such as manganese and iron. The biochemical selection of manganese over iron presents a particularly intricate problem because manganese is generally present in cells at a lower concentration than iron, while also having a lower predicted complex stability according to the Irving-Williams series (Mn(II) < Fe(II) < Ni(II) < Co(II) < Cu(II) > Zn(II)). Here we show that a heterodinuclear Mn/Fe cofactor with the same primary protein ligands in both metal sites self-assembles from Mn(II) and Fe(II) in vitro, thus diverging from the Irving-Williams series without requiring auxiliary factors such as metallochaperones. Crystallographic, spectroscopic, and computational data demonstrate that one of the two metal sites preferentially binds Fe(II) over Mn(II) as expected, whereas the other site is nonspecific, binding equal amounts of both metals in the absence of oxygen. Oxygen exposure results in further accumulation of the Mn/Fe cofactor, indicating that cofactor assembly is at least a two-step process governed by both the intrinsic metal specificity of the protein scaffold and additional effects exerted during oxygen binding or activation. We further show that the mixed-metal cofactor catalyzes a two-electron oxidation of the protein scaffold, yielding a tyrosine-valine ether cross-link. Theoretical modeling of the reaction by density functional theory suggests a multistep mechanism including a valyl radical intermediate. | |||
Direct observation of structurally encoded metal discrimination and ether bond formation in a heterodinuclear metalloprotein.,Griese JJ, Roos K, Cox N, Shafaat HS, Branca RM, Lehtio J, Graslund A, Lubitz W, Siegbahn PE, Hogbom M Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17189-94. doi:, 10.1073/pnas.1304368110. Epub 2013 Oct 7. PMID:24101498<ref>PMID:24101498</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Geobacillus kaustophilus hta426]] | [[Category: Geobacillus kaustophilus hta426]] | ||
[[Category: Ribonucleoside-diphosphate reductase]] | [[Category: Ribonucleoside-diphosphate reductase]] | ||
[[Category: Griese, J J | [[Category: Griese, J J]] | ||
[[Category: Hogbom, M | [[Category: Hogbom, M]] | ||
[[Category: Fatty acid/long-chain hydrocarbon ligand]] | [[Category: Fatty acid/long-chain hydrocarbon ligand]] | ||
[[Category: Heterodinuclear mn/fe cofactor]] | [[Category: Heterodinuclear mn/fe cofactor]] | ||
Revision as of 16:07, 21 December 2014
R2-like ligand-binding oxidase with aerobically reconstituted metal cofactorR2-like ligand-binding oxidase with aerobically reconstituted metal cofactor
Structural highlights
Publication Abstract from PubMedAlthough metallocofactors are ubiquitous in enzyme catalysis, how metal binding specificity arises remains poorly understood, especially in the case of metals with similar primary ligand preferences such as manganese and iron. The biochemical selection of manganese over iron presents a particularly intricate problem because manganese is generally present in cells at a lower concentration than iron, while also having a lower predicted complex stability according to the Irving-Williams series (Mn(II) < Fe(II) < Ni(II) < Co(II) < Cu(II) > Zn(II)). Here we show that a heterodinuclear Mn/Fe cofactor with the same primary protein ligands in both metal sites self-assembles from Mn(II) and Fe(II) in vitro, thus diverging from the Irving-Williams series without requiring auxiliary factors such as metallochaperones. Crystallographic, spectroscopic, and computational data demonstrate that one of the two metal sites preferentially binds Fe(II) over Mn(II) as expected, whereas the other site is nonspecific, binding equal amounts of both metals in the absence of oxygen. Oxygen exposure results in further accumulation of the Mn/Fe cofactor, indicating that cofactor assembly is at least a two-step process governed by both the intrinsic metal specificity of the protein scaffold and additional effects exerted during oxygen binding or activation. We further show that the mixed-metal cofactor catalyzes a two-electron oxidation of the protein scaffold, yielding a tyrosine-valine ether cross-link. Theoretical modeling of the reaction by density functional theory suggests a multistep mechanism including a valyl radical intermediate. Direct observation of structurally encoded metal discrimination and ether bond formation in a heterodinuclear metalloprotein.,Griese JJ, Roos K, Cox N, Shafaat HS, Branca RM, Lehtio J, Graslund A, Lubitz W, Siegbahn PE, Hogbom M Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17189-94. doi:, 10.1073/pnas.1304368110. Epub 2013 Oct 7. PMID:24101498[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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