4lrl: Difference between revisions
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==Structure of an Enterococcus Faecalis HD-domain protein complexed with dGTP and dTTP== | |||
<StructureSection load='4lrl' size='340' side='right' caption='[[4lrl]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4lrl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Entfa Entfa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LRL FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o6i|2o6i]], [[3irh|3irh]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EF-1143, EF_1143 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=226185 ENTFA])</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=4lrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lrl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lrl RCSB], [http://www.ebi.ac.uk/pdbsum/4lrl PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
EF1143 from Enterococcus faecalis, a life-threatening pathogen that is resistant to common antibiotics, is a homo-tetrameric deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase (dNTPase), converting dNTPs into the deoxyribonucleosides and triphosphate. The dNTPase activity of EF1143 is regulated by canonical dNTPs, which simultaneously act as substrates and activity modulators. Previous crystal structures of apo-EF1143 and the protein bound to both dGTP and dATP suggested allosteric regulation of its enzymatic activity by dGTP binding at four identical allosteric sites. However, whether and how other canonical dNTPs regulate the enzyme activity was not defined. Here, we present the crystal structure of EF1143 in complex with dGTP and dTTP. The new structure reveals that the tetrameric EF1143 contains four additional secondary allosteric sites adjacent to the previously identified dGTP-binding primary regulatory sites. Structural and enzyme kinetic studies indicate that dGTP binding to the first allosteric site, with nanomolar affinity, is a prerequisite for substrate docking and hydrolysis. Then, the presence of a particular dNTP in the second site either enhances or inhibits the dNTPase activity of EF1143. Our results provide the first mechanistic insight into dNTP-mediated regulation of dNTPase activity. | |||
Mechanisms of Allosteric Activation and Inhibition of the Deoxyribonucleoside Triphosphate Triphosphohydrolase from Enterococcus faecalis.,Vorontsov II, Wu Y, Delucia M, Minasov G, Mehrens J, Shuvalova L, Anderson WF, Ahn J J Biol Chem. 2014 Jan 31;289(5):2815-24. doi: 10.1074/jbc.M113.524207. Epub 2013 , Dec 12. PMID:24338016<ref>PMID:24338016</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Entfa]] | [[Category: Entfa]] | ||
[[Category: Anderson, W F | [[Category: Anderson, W F]] | ||
[[Category: Joachimiak, A | [[Category: Joachimiak, A]] | ||
[[Category: | [[Category: Structural genomic]] | ||
[[Category: Minasov, G | [[Category: Minasov, G]] | ||
[[Category: Shuvalova, L | [[Category: Shuvalova, L]] | ||
[[Category: Vorontsov, I I | [[Category: Vorontsov, I I]] | ||
[[Category: Allosteric regulation]] | [[Category: Allosteric regulation]] | ||
[[Category: Dntpase]] | [[Category: Dntpase]] | ||
| Line 21: | Line 33: | ||
[[Category: Mcsg]] | [[Category: Mcsg]] | ||
[[Category: Metal binding protein]] | [[Category: Metal binding protein]] | ||
[[Category: Phosphohydrolase]] | [[Category: Phosphohydrolase]] | ||
[[Category: Protein structure initiative | [[Category: PSI, Protein structure initiative]] | ||
Revision as of 12:18, 5 January 2015
Structure of an Enterococcus Faecalis HD-domain protein complexed with dGTP and dTTPStructure of an Enterococcus Faecalis HD-domain protein complexed with dGTP and dTTP
Structural highlights
Publication Abstract from PubMedEF1143 from Enterococcus faecalis, a life-threatening pathogen that is resistant to common antibiotics, is a homo-tetrameric deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase (dNTPase), converting dNTPs into the deoxyribonucleosides and triphosphate. The dNTPase activity of EF1143 is regulated by canonical dNTPs, which simultaneously act as substrates and activity modulators. Previous crystal structures of apo-EF1143 and the protein bound to both dGTP and dATP suggested allosteric regulation of its enzymatic activity by dGTP binding at four identical allosteric sites. However, whether and how other canonical dNTPs regulate the enzyme activity was not defined. Here, we present the crystal structure of EF1143 in complex with dGTP and dTTP. The new structure reveals that the tetrameric EF1143 contains four additional secondary allosteric sites adjacent to the previously identified dGTP-binding primary regulatory sites. Structural and enzyme kinetic studies indicate that dGTP binding to the first allosteric site, with nanomolar affinity, is a prerequisite for substrate docking and hydrolysis. Then, the presence of a particular dNTP in the second site either enhances or inhibits the dNTPase activity of EF1143. Our results provide the first mechanistic insight into dNTP-mediated regulation of dNTPase activity. Mechanisms of Allosteric Activation and Inhibition of the Deoxyribonucleoside Triphosphate Triphosphohydrolase from Enterococcus faecalis.,Vorontsov II, Wu Y, Delucia M, Minasov G, Mehrens J, Shuvalova L, Anderson WF, Ahn J J Biol Chem. 2014 Jan 31;289(5):2815-24. doi: 10.1074/jbc.M113.524207. Epub 2013 , Dec 12. PMID:24338016[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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