5z6w
From Proteopedia
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(New page: '''Unreleased structure''' The entry 5z6w is ON HOLD Authors: Jin, H., Cho, Y. Description: Nuclease Category: Unreleased Structures Category: Cho, Y Category: Jin, H) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of paFAN1 bound to 2nt 5'flap DNA with gap with Manganese== | |
| + | <StructureSection load='5z6w' size='340' side='right'caption='[[5z6w]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5z6w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1] 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=5Z6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z6W 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]] 3.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=5z6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z6w OCA], [https://pdbe.org/5z6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z6w RCSB], [https://www.ebi.ac.uk/pdbsum/5z6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z6w ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FAN1_PSEAE FAN1_PSEAE] Nuclease required for the repair of DNA interstrand cross-links (ICL). Acts as a 5'-3' exonuclease that anchors at a cut end of DNA and cleaves DNA successively at every third nucleotide, allowing to excise an ICL from one strand through flanking incisions. Also has endonuclease activity toward 5'-flaps (PubMed:25319828).[UniProtKB:Q9Y2M0]<ref>PMID:24981866</ref> <ref>PMID:25319828</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | DNA interstrand cross-links (ICLs) block the progress of the replication and transcription machineries and can weaken chromosomal stability, resulting in various diseases. FANCD2-FANCI-associated nuclease (FAN1) is a conserved structure-specific nuclease that unhooks DNA ICLs independently of the Fanconi anemia pathway. Recent structural studies have proposed two different mechanistic features for ICL unhooking by human FAN1: a specific basic pocket that recognizes the terminal phosphate of a 1-nucleotide (nt) 5' flap or FAN1 dimerization. Herein, we show that despite lacking these features, Pseudomonas aeruginosa FAN1 (PaFAN1) cleaves substrates at approximately 3-nt intervals and resolves ICLs. Crystal structures of PaFAN1 bound to various DNA substrates revealed that its conserved basic Arg/Lys patch comprising Arg-228 and Lys-260 recognizes phosphate groups near the 5' terminus of a DNA substrate with a 1-nt flap or a nick. Substitution of Lys-260 did not affect PaFAN1's initial endonuclease activity but significantly decreased its subsequent exonuclease activity and ICL unhooking. The Arg/Lys patch also interacted with phosphates at a 3-nt gap, and this interaction could drive movement of the scissile phosphates into the PaFAN1-active site. In human FAN1, the ICL-resolving activity was not affected by individual disruption of the Arg/Lys patch or basic pocket. However, simultaneous substitution of both FAN1 regions significantly reduced its ICL-resolving activity, suggesting that these two basic regions play a complementary role in ICL repair. On the basis of these findings, we propose a conserved role for two basic regions in FAN1 to guide ICL unhooking and to maintain genomic stability. | ||
| - | + | Structural mechanism of DNA interstrand cross-link unhooking by the bacterial FAN1 nuclease.,Jin H, Roy U, Lee G, Scharer OD, Cho Y J Biol Chem. 2018 Apr 27;293(17):6482-6496. doi: 10.1074/jbc.RA118.002171. Epub, 2018 Mar 7. PMID:29514982<ref>PMID:29514982</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Cho | + | <div class="pdbe-citations 5z6w" style="background-color:#fffaf0;"></div> |
| - | [[Category: Jin | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Pseudomonas aeruginosa PAO1]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Cho Y]] | ||
| + | [[Category: Jin H]] | ||
Current revision
Crystal structure of paFAN1 bound to 2nt 5'flap DNA with gap with Manganese
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