View source for 5zog


==Crystal Structure of R192F hFen1 in complex with DNA==
<StructureSection load='5zog' size='340' side='right'caption='[[5zog]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zog]] is a 4 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=5ZOG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZOG 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]] 2.299&#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=5zog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zog OCA], [https://pdbe.org/5zog PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zog RCSB], [https://www.ebi.ac.uk/pdbsum/5zog PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zog ProSAT]</span></td></tr>
</table>
== Function ==
[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 ==
Human flap endonuclease 1 (hFEN1) is a structure-specific nuclease essential for DNA replication and repair processes. hFEN1 has 5' flap removal activity, as well as gap endonuclease activity that is critical for restarting stalled replication forks. Here, we report the crystal structures of wild-type and mutant hFEN1 proteins in complex with DNA substrates, followed by mutagenesis studies that provide mechanistic insight into the protein-protein interactions of hFEN1. We found that in an alpha-helix forming the helical gateway of hFEN1 recognizes the 5' flap prior to its threading into the active site for cleavage. We also found that the beta-pin region is rigidified into a short helix in R192F hFEN1-DNA structures, suppressing its gap endonuclease activity and cycle-dependent kinase interactions. Our findings suggest that a single mutation at the primary methylation site can alter the function of hFEN1 and provide insight into the role of the beta-pin region in hFEN1 protein interactions that are essential for DNA replication and repair.

Structural basis of 5' flap recognition and protein-protein interactions of human flap endonuclease 1.,Xu H, Shi R, Han W, Cheng J, Xu X, Cheng K, Wang L, Tian B, Zheng L, Shen B, Hua Y, Zhao Y Nucleic Acids Res. 2018 Nov 30;46(21):11315-11325. doi: 10.1093/nar/gky911. PMID:30295841<ref>PMID:30295841</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 5zog" style="background-color:#fffaf0;"></div>

==See Also==
*[[Endonuclease 3D structures|Endonuclease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Han W]]
[[Category: Hua Y]]
[[Category: Zhao Y]]