4xp7: Difference between revisions

Revision as of 17:46, 26 April 2023

Crystal structure of Human tRNA dihydrouridine synthase 2

Structural highlights

4xp7 is a 1 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:	CSO, FNR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DUS2L_HUMAN Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.^[1] ^[2]

Publication Abstract from PubMed

The reduction of uridine to dihydrouridine at specific positions in tRNA is catalysed by dihydrouridine synthase (Dus) enzymes. Increased expression of human dihydrouridine synthase 2 (hDus2) has been linked to pulmonary carcinogenesis, while its knockdown decreased cancer cell line viability, suggesting that it may serve as a valuable target for therapeutic intervention. Here, the X-ray crystal structure of a construct of hDus2 encompassing the catalytic and tRNA-recognition domains (residues 1-340) determined at 1.9 A resolution is presented. It is shown that the structure can be determined automatically by phenix.mr_rosetta starting from a bacterial Dus enzyme with only 18% sequence identity and a significantly divergent structure. The overall fold of the human Dus2 is similar to that of bacterial enzymes, but has a larger recognition domain and a unique three-stranded antiparallel beta-sheet insertion into the catalytic domain that packs next to the recognition domain, contributing to domain-domain interactions. The structure may inform the development of novel therapeutic approaches in the fight against lung cancer.

From bacterial to human dihydrouridine synthase: automated structure determination.,Whelan F, Jenkins HT, Griffiths SC, Byrne RT, Dodson EJ, Antson AA Acta Crystallogr D Biol Crystallogr. 2015 Jul 1;71(Pt 7):1564-71. doi:, 10.1107/S1399004715009220. Epub 2015 Jun 30. PMID:26143927^[3]

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

References

↑ Kato T, Daigo Y, Hayama S, Ishikawa N, Yamabuki T, Ito T, Miyamoto M, Kondo S, Nakamura Y. A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis. Cancer Res. 2005 Jul 1;65(13):5638-46. PMID:15994936 doi:https://dx.doi.org/65/13/5638
↑ Mittelstadt M, Frump A, Khuu T, Fowlkes V, Handy I, Patel CV, Patel RC. Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR. Nucleic Acids Res. 2008 Feb;36(3):998-1008. Epub 2007 Dec 20. PMID:18096616 doi:https://dx.doi.org/10.1093/nar/gkm1129
↑ Whelan F, Jenkins HT, Griffiths SC, Byrne RT, Dodson EJ, Antson AA. From bacterial to human dihydrouridine synthase: automated structure determination. Acta Crystallogr D Biol Crystallogr. 2015 Jul 1;71(Pt 7):1564-71. doi:, 10.1107/S1399004715009220. Epub 2015 Jun 30. PMID:26143927 doi:https://dx.doi.org/10.1107/S1399004715009220

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OCA

[1] Kato T, Daigo Y, Hayama S, Ishikawa N, Yamabuki T, Ito T, Miyamoto M, Kondo S, Nakamura Y. A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis. Cancer Res. 2005 Jul 1;65(13):5638-46. PMID:15994936 doi:https://dx.doi.org/65/13/5638

[2] Mittelstadt M, Frump A, Khuu T, Fowlkes V, Handy I, Patel CV, Patel RC. Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR. Nucleic Acids Res. 2008 Feb;36(3):998-1008. Epub 2007 Dec 20. PMID:18096616 doi:https://dx.doi.org/10.1093/nar/gkm1129

[3] Whelan F, Jenkins HT, Griffiths SC, Byrne RT, Dodson EJ, Antson AA. From bacterial to human dihydrouridine synthase: automated structure determination. Acta Crystallogr D Biol Crystallogr. 2015 Jul 1;71(Pt 7):1564-71. doi:, 10.1107/S1399004715009220. Epub 2015 Jun 30. PMID:26143927 doi:https://dx.doi.org/10.1107/S1399004715009220

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='4xp7' size='340' side='right'caption='[[4xp7]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xp7]] is a 1 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=4XP7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XP7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xp7]] is a 1 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=4XP7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XP7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FNR:1-DEOXY-1-(7,8-DIMETHYL-2,4-DIOXO-3,4-DIHYDRO-2H-BENZO[G]PTERIDIN-1-ID-10(5H)-YL)-5-O-PHOSPHONATO-D-RIBITOL'>FNR</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=FNR:1-DEOXY-1-(7,8-DIMETHYL-2,4-DIOXO-3,4-DIHYDRO-2H-BENZO[G]PTERIDIN-1-ID-10(5H)-YL)-5-O-PHOSPHONATO-D-RIBITOL'>FNR</scene></td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></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=4xp7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xp7 OCA], [https://pdbe.org/4xp7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xp7 RCSB], [https://www.ebi.ac.uk/pdbsum/4xp7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xp7 ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUS2, DUS2L ([http://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=4xp7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xp7 OCA], [http://pdbe.org/4xp7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xp7 RCSB], [http://www.ebi.ac.uk/pdbsum/4xp7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xp7 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DUS2L_HUMAN DUS2L_HUMAN]] Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.<ref>PMID:15994936</ref> <ref>PMID:18096616</ref>
+[https://www.uniprot.org/uniprot/DUS2L_HUMAN DUS2L_HUMAN] Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.<ref>PMID:15994936</ref> <ref>PMID:18096616</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Antson, A A]]
+[[Category: Antson AA]]
-[[Category: Byrne, R T]]
+[[Category: Byrne RT]]
-[[Category: Dodson, E J]]
+[[Category: Dodson EJ]]
-[[Category: Griffiths, S]]
+[[Category: Griffiths S]]
-[[Category: Jenkins, H T]]
+[[Category: Jenkins HT]]
-[[Category: Whelan, F]]
+[[Category: Whelan F]]
-[[Category: Dus]]
-[[Category: Oxidoreductase]]
-[[Category: Trna]]

4xp7: Difference between revisions

Revision as of 17:46, 26 April 2023

Crystal structure of Human tRNA dihydrouridine synthase 2

Structural highlights

Function

Publication Abstract from PubMed

References

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