Sandbox Reserved 967

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 41: Line 41:
The β6-α6 loop of the H2A protein could play a role in substrate recognition: the minor groove of the double helix molecule straddles this area of the protein, which results in a non-sequence specific cleavage by the enzyme. Moreover, the β6-α6 loop contains a Lysine amino acid in position 128, which might act as a sensor for the hybrid by forming an interaction with the 2’-hydroxyl group of the ribose in the 3’ nucleotide of the RNA primer in the RNA-DNA hybrid<ref name="ref5"> ('''Figure 2'''). Therefore, since DNA does not contain a 2’-hydroxyl group in it nucleotide sequence, the RNase H2 can only recognize RNA in the hybrid: only ribonucleotides of the RNA strand are positioned in the active site. The RNA-DNA hybrid is placed such that the target phosphodiester bond between the RNA and DNA parts of the hybrid is in the proper orientation for nucleophile attack by a two-metal ion mechanism.
The β6-α6 loop of the H2A protein could play a role in substrate recognition: the minor groove of the double helix molecule straddles this area of the protein, which results in a non-sequence specific cleavage by the enzyme. Moreover, the β6-α6 loop contains a Lysine amino acid in position 128, which might act as a sensor for the hybrid by forming an interaction with the 2’-hydroxyl group of the ribose in the 3’ nucleotide of the RNA primer in the RNA-DNA hybrid<ref name="ref5"> ('''Figure 2'''). Therefore, since DNA does not contain a 2’-hydroxyl group in it nucleotide sequence, the RNase H2 can only recognize RNA in the hybrid: only ribonucleotides of the RNA strand are positioned in the active site. The RNA-DNA hybrid is placed such that the target phosphodiester bond between the RNA and DNA parts of the hybrid is in the proper orientation for nucleophile attack by a two-metal ion mechanism.
It is important to notice that the Mammalian RNase H2 contains only one cleft with the active site for substrate binding: RNase H2 may recognize single ribonucleotide within a DNA duplex that have a B-form helical structure, as well as longer RNA in RNA-DNA hybrid which adopts intermediate A/B form structure. Thus, the RNase H2 enzyme needs to bind both conformations to able to fully complete all its roles.
It is important to notice that the Mammalian RNase H2 contains only one cleft with the active site for substrate binding: RNase H2 may recognize single ribonucleotide within a DNA duplex that have a B-form helical structure, as well as longer RNA in RNA-DNA hybrid which adopts intermediate A/B form structure. Thus, the RNase H2 enzyme needs to bind both conformations to able to fully complete all its roles.
- 
== Activity ==
== Activity ==

Revision as of 17:45, 8 January 2015

This Sandbox is Reserved from 15/11/2014, through 15/05/2015 for use in the course "Biomolecule" taught by Bruno Kieffer at the Strasbourg University. This reservation includes Sandbox Reserved 951 through Sandbox Reserved 975.
To get started:
  • Click the edit this page tab at the top. Save the page after each step, then edit it again.
  • Click the 3D button (when editing, above the wikitext box) to insert Jmol.
  • show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page.
  • Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc.

More help: Help:Editing

Structure of the Mouse RNase H2 Complex

PDB ID 3kio

Drag the structure with the mouse to rotate

References

  1. ↑ http://genome-euro.ucsc.edu/cgi-bin/hgTracks?clade=mammal&org=Mouse&db=mm10&position=RnaseH2&hgt.positionInput=RnaseH2&hgt.suggestTrack=knownGene&Submit=submit&hgsid=201143152_yP1Xd4bMnHS7DV0d3VcqpDSxzzuQ&pix=1563
  2. ↑ Rychlik, Monika P., Hyongi Chon, Susana M. Cerritelli, Paulina Klimek, Robert J. Crouch, and Marcin Nowotny. “Crystal Structures of RNase H2 in Complex with Nucleic Acid Reveal the Mechanism of RNA-DNA Junction Recognition and Cleavage.” Molecular Cell 40, no. 4 (November 24, 2010): 658–70. doi:10.1016/j.molcel.2010.11.001.
  3. ↑ Sparks, Justin L., Hyongi Chon, Susana M. Cerritelli, Thomas A. Kunkel, Erik Johansson, Robert J. Crouch, and Peter M. Burgers. “RNase H2-Initiated Ribonucleotide Excision Repair.” Molecular Cell 47, no. 6 (September 28, 2012): 980–86. doi:10.1016/j.molcel.2012.06.035.
  4. ↑ 4.0 4.1 4.2 Bubeck, Doryen, Martin A. M. Reijns, Stephen C. Graham, Katy R. Astell, E. Yvonne Jones, and Andrew P. Jackson. “PCNA Directs Type 2 RNase H Activity on DNA Replication and Repair Substrates.” Nucleic Acids Research 39, no. 9 (May 2011): 3652–66. doi:10.1093/nar/gkq980.
  5. ↑ 5.0 5.1 Shaban, Nadine M., Scott Harvey, Fred W. Perrino, and Thomas Hollis. “The Structure of the Mammalian RNase H2 Complex Provides Insight into RNA•DNA Hybrid Processing to Prevent Immune Dysfunction.” Journal of Biological Chemistry 285, no. 6 (February 5, 2010): 3617–24. doi:10.1074/jbc.M109.059048.
  6. ↑ http://www.uniprot.org/uniprot/Q9CWY8
  7. ↑ http://www.uniprot.org/uniprot/Q80ZV0
  8. ↑ http://www.uniprot.org/uniprot/Q9CQ18
  9. ↑ Nicholson, Allen W. Ribonucleases. Springer Science & Business Media, 2011.
Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_Reserved_967"
Personal tools