6v63

From Proteopedia

(Difference between revisions)

Current revision

SETD3 WT in Complex with an Actin Peptide with His73 Replaced with Glutamine

Structural highlights

6v63 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.02Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ACTG_HUMAN Baraitser-Winter syndrome;Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

ACTG_HUMAN Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Publication Abstract from PubMed

Most characterized SET domain (SETD) proteins are protein lysine methyltransferases, but SETD3 was recently demonstrated to be a protein (i.e.actin) histidine-N3methyltransferase. Human SETD3 shares a high structural homology with two known protein lysine methyltransferases-human SETD6 and the plant LSMT-but differs in the residues constituting the active site. In the SETD3 active site, Asn-255 engages in a unique hydrogen-bonding interaction with the target histidine of actin that likely contributes to its >1300-fold greater catalytic efficiency (kcat/Km) on histidine than on lysine. Here, we engineered active-site variants to switch the SETD3 target specificity from histidine to lysine. Substitution of Asn-255 with phenylalanine (N255F), together with substitution of Trp-273 with alanine (W273A), generated an active site mimicking that of known lysine methyltransferases. The doubly substituted SETD3 variant exhibited a 13-fold preference for lysine over histidine. We show, by means of X-ray crystallography, that the two target nitrogen atoms-the N3atom of histidine and the terminal e-amino nitrogen of lysine-occupy the same position and point towards and are within a short distance of the incoming methyl group of SAM for a direct methyl transfer during catalysis. In contrast, SETD3 and its Asn-255 substituted derivatives did not methylate glutamine (another potentially methylated amino acid). However, the glutamine-containing peptide competed with the substrate peptide, and glutamine bound in the active site, but too far away from SAM to be methylated. Our results provide insight into the structural parameters defining the target amino acid specificity of SET enzymes.

An engineered variant of SETD3 methyltransferase alters target specificity from histidine to lysine methylation.,Dai S, Horton JR, Wilkinson AW, Gozani O, Zhang X, Cheng X J Biol Chem. 2020 Jan 7. pii: RA119.012319. doi: 10.1074/jbc.RA119.012319. PMID:31911441^[1]

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

References

↑ Dai S, Horton JR, Wilkinson AW, Gozani O, Zhang X, Cheng X. An engineered variant of SETD3 methyltransferase alters target specificity from histidine to lysine methylation. J Biol Chem. 2020 Jan 7. pii: RA119.012319. doi: 10.1074/jbc.RA119.012319. PMID:31911441 doi:http://dx.doi.org/10.1074/jbc.RA119.012319

1 Structural highlights
2 Disease
3 Function
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/6v63"

Categories: Homo sapiens | Large Structures | Cheng X | Dai S | Horton JR

@@ Line 3: / Line 3: @@
 <StructureSection load='6v63' size='340' side='right'caption='[[6v63]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6v63]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V63 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V63 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6v63]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V63 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V63 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.02&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-histidine_N-methyltransferase Protein-histidine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.85 2.1.1.85] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></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=6v63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v63 OCA], [http://pdbe.org/6v63 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v63 RCSB], [http://www.ebi.ac.uk/pdbsum/6v63 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v63 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=6v63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v63 OCA], [https://pdbe.org/6v63 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v63 RCSB], [https://www.ebi.ac.uk/pdbsum/6v63 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v63 ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ACTG_HUMAN ACTG_HUMAN] Baraitser-Winter syndrome;Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/SETD3_HUMAN SETD3_HUMAN]] Histone methyltransferase that methylates 'Lys-36' of histone H3 (H3K36me). H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation (By similarity).
+[https://www.uniprot.org/uniprot/ACTG_HUMAN ACTG_HUMAN] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 21: @@
 </div>
 <div class="pdbe-citations 6v63" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Protein-histidine N-methyltransferase]]
+[[Category: Cheng X]]
-[[Category: Cheng, X]]
+[[Category: Dai S]]
-[[Category: Dai, S]]
+[[Category: Horton JR]]
-[[Category: Horton, J R]]
-[[Category: Transferase]]
-[[Category: Transferase-structural protein complex]]

6v63

From Proteopedia

Current revision

SETD3 WT in Complex with an Actin Peptide with His73 Replaced with Glutamine

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox