2le2: Difference between revisions
No edit summary |
No edit summary |
||
| (10 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Novel dimeric structure of phage phi29-encoded protein p56: Insights into Uracil-DNA glycosylase inhibition== | |||
<StructureSection load='2le2' size='340' side='right'caption='[[2le2]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2le2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_virus_phi29 Bacillus virus phi29]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LE2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2le2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2le2 OCA], [https://pdbe.org/2le2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2le2 RCSB], [https://www.ebi.ac.uk/pdbsum/2le2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2le2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/P56_BPPH2 P56_BPPH2] Inhibits the host uracil-DNA glycosylase (UDG), an enzyme which removes uracil residues from DNA by the base excision repair. Interacts with host uracil-DNA glycosylase and prevents the latter from binding to DNA. Since the viral DNA polymerase efficiently incorporates dUMP into DNA, the virus needs to prevent the deleterious effect caused by host UDG when it eliminates uracil residues present in the viral genome.<ref>PMID:17698500</ref> <ref>PMID:18845683</ref> <ref>PMID:21542855</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein p56 encoded by the Bacillus subtilis phage 29 inhibits the host uracil-DNA glycosylase (UDG) activity. To get insights into the structural basis for this inhibition, the NMR solution structure of p56 has been determined. The inhibitor defines a novel dimeric fold, stabilized by a combination of polar and extensive hydrophobic interactions. Each polypeptide chain contains three stretches of anti-parallel beta-sheets and a helical region linked by three short loops. In addition, microcalorimetry titration experiments showed that it forms a tight 2:1 complex with UDG, strongly suggesting that the dimer represents the functional form of the inhibitor. This was further confirmed by the functional analysis of p56 mutants unable to assemble into dimers. We have also shown that the highly anionic region of the inhibitor plays a significant role in the inhibition of UDG. Thus, based on these findings and taking into account previous results that revealed similarities between the association mode of p56 and the phage PBS-1/PBS-2-encoded inhibitor Ugi with UDG, we propose that protein p56 might inhibit the enzyme by mimicking its DNA substrate. | |||
Novel dimeric structure of phage {phi}29-encoded protein p56: insights into uracil-DNA glycosylase inhibition.,Asensio JL, Perez-Lago L, Lazaro JM, Gonzalez C, Serrano-Heras G, Salas M Nucleic Acids Res. 2011 Sep 2. PMID:21890898<ref>PMID:21890898</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2le2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacillus virus phi29]] | |||
[[Category: Large Structures]] | |||
[[Category: Asensio J]] | |||
[[Category: Gonzalez C]] | |||
[[Category: Lazaro JM]] | |||
[[Category: Perez-Lago L]] | |||
[[Category: Salas M]] | |||
[[Category: Serrano-Heras G]] | |||
Latest revision as of 08:42, 15 May 2024
Novel dimeric structure of phage phi29-encoded protein p56: Insights into Uracil-DNA glycosylase inhibitionNovel dimeric structure of phage phi29-encoded protein p56: Insights into Uracil-DNA glycosylase inhibition
Structural highlights
FunctionP56_BPPH2 Inhibits the host uracil-DNA glycosylase (UDG), an enzyme which removes uracil residues from DNA by the base excision repair. Interacts with host uracil-DNA glycosylase and prevents the latter from binding to DNA. Since the viral DNA polymerase efficiently incorporates dUMP into DNA, the virus needs to prevent the deleterious effect caused by host UDG when it eliminates uracil residues present in the viral genome.[1] [2] [3] Publication Abstract from PubMedProtein p56 encoded by the Bacillus subtilis phage 29 inhibits the host uracil-DNA glycosylase (UDG) activity. To get insights into the structural basis for this inhibition, the NMR solution structure of p56 has been determined. The inhibitor defines a novel dimeric fold, stabilized by a combination of polar and extensive hydrophobic interactions. Each polypeptide chain contains three stretches of anti-parallel beta-sheets and a helical region linked by three short loops. In addition, microcalorimetry titration experiments showed that it forms a tight 2:1 complex with UDG, strongly suggesting that the dimer represents the functional form of the inhibitor. This was further confirmed by the functional analysis of p56 mutants unable to assemble into dimers. We have also shown that the highly anionic region of the inhibitor plays a significant role in the inhibition of UDG. Thus, based on these findings and taking into account previous results that revealed similarities between the association mode of p56 and the phage PBS-1/PBS-2-encoded inhibitor Ugi with UDG, we propose that protein p56 might inhibit the enzyme by mimicking its DNA substrate. Novel dimeric structure of phage {phi}29-encoded protein p56: insights into uracil-DNA glycosylase inhibition.,Asensio JL, Perez-Lago L, Lazaro JM, Gonzalez C, Serrano-Heras G, Salas M Nucleic Acids Res. 2011 Sep 2. PMID:21890898[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||