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3k9j

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Revision as of 12:26, 25 December 2014

Transposase domain of Metnase

Structural highlights

3k9j is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3k9k
Gene:	SETMAR (Homo sapiens)
Activity:	Histone-lysine N-methyltransferase, with EC number 2.1.1.43
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[SETMR_HUMAN] Histone methyltransferase that methylates 'Lys-4' and 'Lys-36' of histone H3, 2 specific tags for epigenetic transcriptional activation. Specifically mediates dimethylation of H3 'Lys-36'. Has sequence-specific DNA-binding activity and recognizes the 19-mer core of the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element. Has DNA nicking activity. Has in vivo end joining activity and may mediate genomic integration of foreign DNA.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Although the human genome is littered with sequences derived from the Hsmar1 transposon, the only intact Hsmar1 transposase gene exists within a chimeric SET-transposase fusion protein referred to as Metnase or SETMAR. Metnase retains many of the transposase activities including terminal inverted repeat (TIR) specific DNA-binding activity, DNA cleavage activity, albeit uncoupled from TIR-specific binding, and the ability to form a synaptic complex. However, Metnase has evolved as a DNA repair protein that is specifically involved in nonhomologous end joining. Here, we present two crystal structures of the transposase catalytic domain of Metnase revealing a dimeric enzyme with unusual active site plasticity that may be involved in modulating metal binding. We show through characterization of a dimerization mutant, F460K, that the dimeric form of the enzyme is required for its DNA cleavage, DNA-binding, and nonhomologous end joining activities. Of significance is the conservation of F460 along with residues that we propose may be involved in the modulation of metal binding in both the predicted ancestral Hsmar1 transposase sequence as well as in the modern enzyme. The Metnase transposase has been remarkably conserved through evolution; however, there is a clustering of substitutions located in alpha helices 4 and 5 within the putative DNA-binding site, consistent with loss of transposition specific DNA cleavage activity and acquisition of DNA repair specific cleavage activity.

Crystal structure of the human Hsmar1-derived transposase domain in the DNA repair enzyme Metnase.,Goodwin KD, He H, Imasaki T, Lee SH, Georgiadis MM Biochemistry. 2010 Jul 13;49(27):5705-13. PMID:20521842^[5]

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

References

↑ Lee SH, Oshige M, Durant ST, Rasila KK, Williamson EA, Ramsey H, Kwan L, Nickoloff JA, Hromas R. The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair. Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18075-80. Epub 2005 Dec 6. PMID:16332963 doi:10.1073/pnas.0503676102
↑ Cordaux R, Udit S, Batzer MA, Feschotte C. Birth of a chimeric primate gene by capture of the transposase gene from a mobile element. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8101-6. Epub 2006 May 3. PMID:16672366 doi:0601161103
↑ Roman Y, Oshige M, Lee YJ, Goodwin K, Georgiadis MM, Hromas RA, Lee SH. Biochemical characterization of a SET and transposase fusion protein, Metnase: its DNA binding and DNA cleavage activity. Biochemistry. 2007 Oct 9;46(40):11369-76. Epub 2007 Sep 18. PMID:17877369 doi:10.1021/bi7005477
↑ Miskey C, Papp B, Mates L, Sinzelle L, Keller H, Izsvak Z, Ivics Z. The ancient mariner sails again: transposition of the human Hsmar1 element by a reconstructed transposase and activities of the SETMAR protein on transposon ends. Mol Cell Biol. 2007 Jun;27(12):4589-600. Epub 2007 Apr 2. PMID:17403897 doi:10.1128/MCB.02027-06
↑ Goodwin KD, He H, Imasaki T, Lee SH, Georgiadis MM. Crystal structure of the human Hsmar1-derived transposase domain in the DNA repair enzyme Metnase. Biochemistry. 2010 Jul 13;49(27):5705-13. PMID:20521842 doi:10.1021/bi100171x

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3k9j"

@@ Line 9: / Line 9: @@
 <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=3k9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k9j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3k9j RCSB], [http://www.ebi.ac.uk/pdbsum/3k9j PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/SETMR_HUMAN SETMR_HUMAN]] Histone methyltransferase that methylates 'Lys-4' and 'Lys-36' of histone H3, 2 specific tags for epigenetic transcriptional activation. Specifically mediates dimethylation of H3 'Lys-36'. Has sequence-specific DNA-binding activity and recognizes the 19-mer core of the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element. Has DNA nicking activity. Has in vivo end joining activity and may mediate genomic integration of foreign DNA.<ref>PMID:16332963</ref> <ref>PMID:16672366</ref> <ref>PMID:17877369</ref> <ref>PMID:17403897</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3k9j

From Proteopedia

Revision as of 12:26, 25 December 2014

Transposase domain of Metnase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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