3qe9

From Proteopedia
Revision as of 09:04, 8 June 2022 by OCA (talk | contribs)
Jump to navigation Jump to search

Crystal structure of human exonuclease 1 Exo1 (D173A) in complex with DNA (complex I)Crystal structure of human exonuclease 1 Exo1 (D173A) in complex with DNA (complex I)

Structural highlights

3qe9 is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
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.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ Genschel J, Modrich P. Mechanism of 5'-directed excision in human mismatch repair. Mol Cell. 2003 Nov;12(5):1077-86. PMID:14636568
  8. ↑ 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
  9. ↑ 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
  10. ↑ 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
  11. ↑ 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
  12. ↑ 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
  13. ↑ 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

3qe9, resolution 2.51Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3qe9&oldid=3570066"