5k97: Difference between revisions

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 ==Flap endonuclease 1 (FEN1) D233N with cleaved product fragment and Sm3+==
-<StructureSection load='5k97' size='340' side='right' caption='[[5k97]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='5k97' size='340' side='right'caption='[[5k97]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5k97]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K97 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K97 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5k97]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=5K97 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K97 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SM:SAMARIUM+(III)+ION'>SM</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.102&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5k96|5k96]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SM:SAMARIUM+(III)+ION'>SM</scene></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=5k97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k97 OCA], [http://pdbe.org/5k97 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k97 RCSB], [http://www.ebi.ac.uk/pdbsum/5k97 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k97 ProSAT]</span></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=5k97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k97 OCA], [https://pdbe.org/5k97 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k97 RCSB], [https://www.ebi.ac.uk/pdbsum/5k97 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k97 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/FEN1_HUMAN FEN1_HUMAN]] Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.<ref>PMID:7961795</ref> <ref>PMID:8621570</ref> <ref>PMID:10744741</ref> <ref>PMID:11986308</ref> <ref>PMID:18443037</ref> <ref>PMID:20729856</ref>
+[https://www.uniprot.org/uniprot/FEN1_HUMAN FEN1_HUMAN] Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.<ref>PMID:7961795</ref> <ref>PMID:8621570</ref> <ref>PMID:10744741</ref> <ref>PMID:11986308</ref> <ref>PMID:18443037</ref> <ref>PMID:20729856</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 5'-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 5'-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 5'polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via 'phosphate steering', basic residues energetically steer an inverted ss 5'-flap through a gateway over FEN1's active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 5'-flap specificity and catalysis, preventing genomic instability.
-Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.,Tsutakawa SE, Thompson MJ, Arvai AS, Neil AJ, Shaw SJ, Algasaier SI, Kim JC, Finger LD, Jardine E, Gotham VJB, Sarker AH, Her MZ, Rashid F, Hamdan SM, Mirkin SM, Grasby JA, Tainer JA Nat Commun. 2017 Jun 27;8:15855. doi: 10.1038/ncomms15855. PMID:28653660<ref>PMID:28653660</ref>
+==See Also==
+*[[Endonuclease 3D structures|Endonuclease 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 5k97" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Arvai, A S]]
+[[Category: Homo sapiens]]
-[[Category: Tainer, J A]]
+[[Category: Large Structures]]
-[[Category: Tsutakawa, S E]]
+[[Category: Synthetic construct]]
-[[Category: 5' nuclease]]
+[[Category: Arvai AS]]
-[[Category: Base excision repair]]
+[[Category: Tainer JA]]
-[[Category: Dna damage]]
+[[Category: Tsutakawa SE]]
-[[Category: Dna repair]]
-[[Category: Fen]]
-[[Category: Hydrolase-dna complex]]
-[[Category: Metalloprotein]]
-[[Category: Product]]
-[[Category: Protein-dna]]
-[[Category: Replication]]