6d9q: Difference between revisions
m Protected "6d9q" [edit=sysop:move=sysop] |
No edit summary |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==The sulfate-bound crystal structure of HPRT (hypoxanthine phosphoribosyltransferase)== | ||
<StructureSection load='6d9q' size='340' side='right'caption='[[6d9q]], [[Resolution|resolution]] 2.06Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6d9q]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D9Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D9Q FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.056Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6d9q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d9q OCA], [https://pdbe.org/6d9q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d9q RCSB], [https://www.ebi.ac.uk/pdbsum/6d9q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d9q ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/B9ZW32_BACAN B9ZW32_BACAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The alarmone (p)ppGpp regulates diverse targets, yet its target specificity and evolution remain poorly understood. Here, we elucidate the mechanism by which basal (p)ppGpp inhibits the purine salvage enzyme HPRT by sharing a conserved motif with its substrate PRPP. Intriguingly, HPRT regulation by (p)ppGpp varies across organisms and correlates with HPRT oligomeric forms. (p)ppGpp-sensitive HPRT exists as a PRPP-bound dimer or an apo- and (p)ppGpp-bound tetramer, where a dimer-dimer interface triggers allosteric structural rearrangements to enhance (p)ppGpp inhibition. Loss of this oligomeric interface results in weakened (p)ppGpp regulation. Our results reveal an evolutionary principle whereby protein oligomerization allows evolutionary change to accumulate away from a conserved binding pocket to allosterically alter specificity of ligand interaction. This principle also explains how another (p)ppGpp target GMK is variably regulated across species. Since most ligands bind near protein interfaces, we propose that this principle extends to many other protein-ligand interactions. | |||
Evolution of (p)ppGpp-HPRT regulation through diversification of an allosteric oligomeric interaction.,Anderson BW, Liu K, Wolak C, Dubiel K, She F, Satyshur KA, Keck JL, Wang JD Elife. 2019 Sep 25;8. pii: 47534. doi: 10.7554/eLife.47534. PMID:31552824<ref>PMID:31552824</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6d9q" style="background-color:#fffaf0;"></div> | ||
[[Category: Anderson | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacillus anthracis]] | |||
[[Category: Large Structures]] | |||
[[Category: Anderson B]] | |||
[[Category: Dubiel K]] | |||
[[Category: Keck JL]] | |||
[[Category: Satyshur KA]] | |||
[[Category: Wolak C]] | |||
Latest revision as of 18:20, 4 October 2023
The sulfate-bound crystal structure of HPRT (hypoxanthine phosphoribosyltransferase)The sulfate-bound crystal structure of HPRT (hypoxanthine phosphoribosyltransferase)
Structural highlights
FunctionPublication Abstract from PubMedThe alarmone (p)ppGpp regulates diverse targets, yet its target specificity and evolution remain poorly understood. Here, we elucidate the mechanism by which basal (p)ppGpp inhibits the purine salvage enzyme HPRT by sharing a conserved motif with its substrate PRPP. Intriguingly, HPRT regulation by (p)ppGpp varies across organisms and correlates with HPRT oligomeric forms. (p)ppGpp-sensitive HPRT exists as a PRPP-bound dimer or an apo- and (p)ppGpp-bound tetramer, where a dimer-dimer interface triggers allosteric structural rearrangements to enhance (p)ppGpp inhibition. Loss of this oligomeric interface results in weakened (p)ppGpp regulation. Our results reveal an evolutionary principle whereby protein oligomerization allows evolutionary change to accumulate away from a conserved binding pocket to allosterically alter specificity of ligand interaction. This principle also explains how another (p)ppGpp target GMK is variably regulated across species. Since most ligands bind near protein interfaces, we propose that this principle extends to many other protein-ligand interactions. Evolution of (p)ppGpp-HPRT regulation through diversification of an allosteric oligomeric interaction.,Anderson BW, Liu K, Wolak C, Dubiel K, She F, Satyshur KA, Keck JL, Wang JD Elife. 2019 Sep 25;8. pii: 47534. doi: 10.7554/eLife.47534. PMID:31552824[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||