View source for 8gj5


==fungal pcna and peptidomimetic==
<StructureSection load='8gj5' size='340' side='right'caption='[[8gj5]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gj5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GJ5 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]] 2.3&#8491;</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=8gj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gj5 OCA], [https://pdbe.org/8gj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gj5 RCSB], [https://www.ebi.ac.uk/pdbsum/8gj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gj5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A229Y5V5_ASPFM A0A229Y5V5_ASPFM] This protein is an auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand.[RuleBase:RU000641]
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== Publication Abstract from PubMed ==
Invasive fungal infections (IFIs) are prevalent in immunocompromised patients. Due to alarming levels of increasing resistance in clinical settings, new drugs targeting the major fungal pathogen Aspergillus fumigatus are required. Attractive drug targets are those involved in essential processes like DNA replication, such as proliferating cell nuclear antigens (PCNAs). PCNA has been previously studied in cancer research and presents a viable target for antifungals. Human PCNA interacts with the p21 protein, outcompeting binding proteins to halt DNA replication. The affinity of p21 for hPCNA has been shown to outcompete other associating proteins, presenting an attractive scaffold for peptidomimetic design. p21 has no A. fumigatus homolog to our knowledge, yet our group has previously demonstrated that human p21 can interact with A. fumigatus PCNA (afumPCNA). This suggests that a p21-based inhibitor could be designed to outcompete the native binding partners of afumPCNA to inhibit fungal growth. Here, we present an investigation of extensive structure-activity relationships between designed p21-based peptides and afumPCNA and the first crystal structure of a p21 peptide bound to afumPCNA, demonstrating that the A. fumigatus replication model uses a PIP-box sequence as the method for binding to afumPCNA. These results inform the new optimized secondary structure design of a potential peptidomimetic inhibitor of afumPCNA.

Towards a High-Affinity Peptidomimetic Targeting Proliferating Cell Nuclear Antigen from Aspergillus fumigatus.,Vandborg BC, Horsfall AJ, Pederick JL, Abell AD, Bruning JB J Fungi (Basel). 2023 Nov 10;9(11):1098. doi: 10.3390/jof9111098. PMID:37998903<ref>PMID:37998903</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8gj5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Aspergillus fumigatus]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bruning JB]]
[[Category: Vandborg B]]