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3qea

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Revision as of 06:04, 8 June 2022

Crystal structure of human exonuclease 1 Exo1 (WT) in complex with DNA (complex II)

Structural highlights

3qea is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3qe9, 3qeb
Gene:	EXO1, EXOI, HEX1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[EXO1_HUMAN] 5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

Publication Abstract from PubMed

Human exonuclease 1 (hExo1) plays important roles in DNA repair and recombination processes that maintain genomic integrity. It is a member of the 5' structure-specific nuclease family of exonucleases and endonucleases that includes FEN-1, XPG, and GEN1. We present structures of hExo1 in complex with a DNA substrate, followed by mutagenesis studies, and propose a common mechanism by which this nuclease family recognizes and processes diverse DNA structures. hExo1 induces a sharp bend in the DNA at nicks or gaps. Frayed 5' ends of nicked duplexes resemble flap junctions, unifying the mechanisms of endo- and exonucleolytic processing. Conformational control of a mobile region in the catalytic site suggests a mechanism for allosteric regulation by binding to protein partners. The relative arrangement of substrate binding sites in these enzymes provides an elegant solution to a complex geometrical puzzle of substrate recognition and processing.

Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family.,Orans J, McSweeney EA, Iyer RR, Hast MA, Hellinga HW, Modrich P, Beese LS Cell. 2011 Apr 15;145(2):212-23. PMID:21496642^[13]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Qiu J, Qian Y, Chen V, Guan MX, Shen B. Human exonuclease 1 functionally complements its yeast homologues in DNA recombination, RNA primer removal, and mutation avoidance. J Biol Chem. 1999 Jun 18;274(25):17893-900. PMID:10364235
↑ Lee BI, Wilson DM 3rd. The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and flap structure-specific endonuclease activities. J Biol Chem. 1999 Dec 31;274(53):37763-9. PMID:10608837
↑ Genschel J, Bazemore LR, Modrich P. Human exonuclease I is required for 5' and 3' mismatch repair. J Biol Chem. 2002 Apr 12;277(15):13302-11. Epub 2002 Jan 24. PMID:11809771 doi:http://dx.doi.org/10.1074/jbc.M111854200
↑ Lee Bi BI, Nguyen LH, Barsky D, Fernandes M, Wilson DM 3rd. Molecular interactions of human Exo1 with DNA. Nucleic Acids Res. 2002 Feb 15;30(4):942-9. PMID:11842105
↑ Sun X, Zheng L, Shen B. Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome. Cancer Res. 2002 Nov 1;62(21):6026-30. PMID:12414623
↑ Sharma S, Sommers JA, Driscoll HC, Uzdilla L, Wilson TM, Brosh RM Jr. The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein. J Biol Chem. 2003 Jun 27;278(26):23487-96. Epub 2003 Apr 18. PMID:12704184 doi:http://dx.doi.org/10.1074/jbc.M212798200
↑ Genschel J, Modrich P. Mechanism of 5'-directed excision in human mismatch repair. Mol Cell. 2003 Nov;12(5):1077-86. PMID:14636568
↑ Nielsen FC, Jager AC, Lutzen A, Bundgaard JR, Rasmussen LJ. Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA. Oncogene. 2004 Feb 19;23(7):1457-68. PMID:14676842 doi:http://dx.doi.org/10.1038/sj.onc.1207265
↑ Dzantiev L, Constantin N, Genschel J, Iyer RR, Burgers PM, Modrich P. A defined human system that supports bidirectional mismatch-provoked excision. Mol Cell. 2004 Jul 2;15(1):31-41. PMID:15225546 doi:http://dx.doi.org/10.1016/j.molcel.2004.06.016
↑ Doherty KM, Sharma S, Uzdilla LA, Wilson TM, Cui S, Vindigni A, Brosh RM Jr. RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination. J Biol Chem. 2005 Jul 29;280(30):28085-94. Epub 2005 May 9. PMID:15886194 doi:http://dx.doi.org/10.1074/jbc.M500265200
↑ Zhang Y, Yuan F, Presnell SR, Tian K, Gao Y, Tomkinson AE, Gu L, Li GM. Reconstitution of 5'-directed human mismatch repair in a purified system. Cell. 2005 Sep 9;122(5):693-705. PMID:16143102 doi:http://dx.doi.org/10.1016/j.cell.2005.06.027
↑ Wilson DM 3rd, Carney JP, Coleman MA, Adamson AW, Christensen M, Lamerdin JE. Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1. Nucleic Acids Res. 1998 Aug 15;26(16):3762-8. PMID:9685493
↑ Orans J, McSweeney EA, Iyer RR, Hast MA, Hellinga HW, Modrich P, Beese LS. Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family. Cell. 2011 Apr 15;145(2):212-23. PMID:21496642 doi:10.1016/j.cell.2011.03.005

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3qea"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human exonuclease 1 Exo1 (WT) in complex with DNA (complex II)==
-<StructureSection load='3qea' size='340' side='right' caption='[[3qea]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+<StructureSection load='3qea' size='340' side='right'caption='[[3qea]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3qea]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QEA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3qea]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QEA FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BA:BARIUM+ION'>BA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BA:BARIUM+ION'>BA</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qe9|3qe9]], [[3qeb|3qeb]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qe9|3qe9]], [[3qeb|3qeb]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EXO1, EXOI, HEX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EXO1, EXOI, HEX1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3qea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qea OCA], [http://pdbe.org/3qea PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qea RCSB], [http://www.ebi.ac.uk/pdbsum/3qea PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qea 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=3qea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qea OCA], [https://pdbe.org/3qea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qea RCSB], [https://www.ebi.ac.uk/pdbsum/3qea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qea ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/EXO1_HUMAN EXO1_HUMAN]] 5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis.<ref>PMID:10364235</ref> <ref>PMID:10608837</ref> <ref>PMID:11809771</ref> <ref>PMID:11842105</ref> <ref>PMID:12414623</ref> <ref>PMID:12704184</ref> <ref>PMID:14636568</ref> <ref>PMID:14676842</ref> <ref>PMID:15225546</ref> <ref>PMID:15886194</ref> <ref>PMID:16143102</ref> <ref>PMID:9685493</ref>
+[[https://www.uniprot.org/uniprot/EXO1_HUMAN EXO1_HUMAN]] 5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis.<ref>PMID:10364235</ref> <ref>PMID:10608837</ref> <ref>PMID:11809771</ref> <ref>PMID:11842105</ref> <ref>PMID:12414623</ref> <ref>PMID:12704184</ref> <ref>PMID:14636568</ref> <ref>PMID:14676842</ref> <ref>PMID:15225546</ref> <ref>PMID:15886194</ref> <ref>PMID:16143102</ref> <ref>PMID:9685493</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 ==See Also==
-*[[Exonuclease|Exonuclease]]
+*[[Exonuclease 3D structures|Exonuclease 3D structures]]
 == References ==
 <references/>
@@ Line 28: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Beese, L S]]
 [[Category: Hast, M A]]

3qea

From Proteopedia

Revision as of 06:04, 8 June 2022

Crystal structure of human exonuclease 1 Exo1 (WT) in complex with DNA (complex II)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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