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==Crystal structure of Staphylococcal nuclease variant Delta+PHS V23K/L36Q at cryogenic temperature== | ==Crystal structure of Staphylococcal nuclease variant Delta+PHS V23K/L36Q at cryogenic temperature== | ||
<StructureSection load='6b8r' size='340' side='right' caption='[[6b8r]], [[Resolution|resolution]] 1.65Å' scene=''> | <StructureSection load='6b8r' size='340' side='right'caption='[[6b8r]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6b8r]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6b8r]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B8R FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=THP:THYMIDINE-3,5-DIPHOSPHATE'>THP</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6b8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b8r OCA], [https://pdbe.org/6b8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b8r RCSB], [https://www.ebi.ac.uk/pdbsum/6b8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b8r ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/NUC_STAAU NUC_STAAU] Enzyme that catalyzes the hydrolysis of both DNA and RNA at the 5' position of the phosphodiester bond. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Thirty years ago, Hwang and Warshel suggested that a microenvironment preorganized to stabilize an ion pair would be incapable of reorganizing to stabilize the reverse ion pair. The implications were that (1) proteins have a limited capacity to reorganize, even under the influence of strong interactions, such as those present when ionizable groups are buried in the hydrophobic interior of a protein, and (2) the inability of proteins to tolerate the reversal of buried ion pairs demonstrates the limitations inherent to continuum electrostatic models of proteins. Previously we showed that when buried individually in the interior of staphylococcal nuclease, Glu23 and Lys36 have p Ka values near pH 7, but when buried simultaneously, they establish a strong interaction of approximately 5 kcal/mol and have p Ka values shifted toward more normal values. Here, using equilibrium thermodynamic measurements, crystal structures, and NMR spectroscopy experiments, we show that although the reversed, individual substitutions-Lys23 and Glu36-also have p Ka values near 7, when buried together, they neither establish a strong interaction nor promote reorganization of their microenvironment. These experiments both confirm Warshel's original hypothesis and expand it by showing that it applies to reorganization, as demonstrated by our artificial ion pairs, as well as to preorganization as is commonly argued for motifs that stabilize naturally occurring ion pairs in polar microenvironments. These data constitute a challenging benchmark useful to test the ability of structure-based algorithms to reproduce the compensation between self-energy, Coulomb and polar interactions in hydrophobic environments of proteins. | |||
Dielectric Properties of a Protein Probed by Reversal of a Buried Ion Pair.,Robinson AC, Schlessman JL, Garcia-Moreno E B J Phys Chem B. 2018 Mar 8;122(9):2516-2524. doi: 10.1021/acs.jpcb.7b12121. Epub, 2018 Feb 21. PMID:29466010<ref>PMID:29466010</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6b8r" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Staphylococcal nuclease 3D structures|Staphylococcal nuclease 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Benning | [[Category: Staphylococcus aureus]] | ||
[[Category: | [[Category: Benning M]] | ||
[[Category: Robinson | [[Category: Garcia-Moreno E B]] | ||
[[Category: Schlessman | [[Category: Robinson AC]] | ||
[[Category: Schlessman JL]] | |||
Latest revision as of 17:35, 4 October 2023
Crystal structure of Staphylococcal nuclease variant Delta+PHS V23K/L36Q at cryogenic temperatureCrystal structure of Staphylococcal nuclease variant Delta+PHS V23K/L36Q at cryogenic temperature
Structural highlights
FunctionNUC_STAAU Enzyme that catalyzes the hydrolysis of both DNA and RNA at the 5' position of the phosphodiester bond. Publication Abstract from PubMedThirty years ago, Hwang and Warshel suggested that a microenvironment preorganized to stabilize an ion pair would be incapable of reorganizing to stabilize the reverse ion pair. The implications were that (1) proteins have a limited capacity to reorganize, even under the influence of strong interactions, such as those present when ionizable groups are buried in the hydrophobic interior of a protein, and (2) the inability of proteins to tolerate the reversal of buried ion pairs demonstrates the limitations inherent to continuum electrostatic models of proteins. Previously we showed that when buried individually in the interior of staphylococcal nuclease, Glu23 and Lys36 have p Ka values near pH 7, but when buried simultaneously, they establish a strong interaction of approximately 5 kcal/mol and have p Ka values shifted toward more normal values. Here, using equilibrium thermodynamic measurements, crystal structures, and NMR spectroscopy experiments, we show that although the reversed, individual substitutions-Lys23 and Glu36-also have p Ka values near 7, when buried together, they neither establish a strong interaction nor promote reorganization of their microenvironment. These experiments both confirm Warshel's original hypothesis and expand it by showing that it applies to reorganization, as demonstrated by our artificial ion pairs, as well as to preorganization as is commonly argued for motifs that stabilize naturally occurring ion pairs in polar microenvironments. These data constitute a challenging benchmark useful to test the ability of structure-based algorithms to reproduce the compensation between self-energy, Coulomb and polar interactions in hydrophobic environments of proteins. Dielectric Properties of a Protein Probed by Reversal of a Buried Ion Pair.,Robinson AC, Schlessman JL, Garcia-Moreno E B J Phys Chem B. 2018 Mar 8;122(9):2516-2524. doi: 10.1021/acs.jpcb.7b12121. Epub, 2018 Feb 21. PMID:29466010[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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