2xse

From Proteopedia

(Difference between revisions)

Revision as of 12:16, 27 April 2022

The structural basis for recognition of J-base containing DNA by a novel DNA-binding domain in JBP1

Structural highlights

2xse is a 1 chain structure with sequence from Leita. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Activity:	Thymine dioxygenase, with EC number 1.14.11.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[JBP1_LEITA] Dioxygenase that catalyzes the first step of DNA base J (beta-d-glucosyl-HOMedU) biosynthesis by converting thymine to 5-hydroxymethyluracil (HOMedU). DNA base J is a hypermodified thymidine residue found in the genome of kinetoplastid parasites, which is localized primarily to repetitive DNA, namely the telomeres, and is implicated in the regulation of antigenic variation. Also specifically binds to base J-containing DNA (J-DNA). Involved in propagation and maintenance of DNA base J synthesis initiated by JBP2 by specifically binding already synthesized DNA base J and propagating J synthesis. Thymine dioxygenase activity and J-DNA-binding are independent functions.^[1]

Publication Abstract from PubMed

The J-binding protein 1 (JBP1) is essential for biosynthesis and maintenance of DNA base-J (beta-d-glucosyl-hydroxymethyluracil). Base-J and JBP1 are confined to some pathogenic protozoa and are absent from higher eukaryotes, prokaryotes and viruses. We show that JBP1 recognizes J-containing DNA (J-DNA) through a 160-residue domain, DB-JBP1, with 10 000-fold preference over normal DNA. The crystal structure of DB-JBP1 revealed a helix-turn-helix variant fold, a 'helical bouquet' with a 'ribbon' helix encompassing the amino acids responsible for DNA binding. Mutation of a single residue (Asp525) in the ribbon helix abrogates specificity toward J-DNA. The same mutation renders JBP1 unable to rescue the targeted deletion of endogenous JBP1 genes in Leishmania and changes its distribution in the nucleus. Based on mutational analysis and hydrogen/deuterium-exchange mass-spectrometry data, a model of JBP1 bound to J-DNA was constructed and validated by small-angle X-ray scattering data. Our results open new possibilities for targeted prevention of J-DNA recognition as a therapeutic intervention for parasitic diseases.

The structural basis for recognition of base J containing DNA by a novel DNA binding domain in JBP1.,Heidebrecht T, Christodoulou E, Chalmers MJ, Jan S, Ter Riet B, Grover RK, Joosten RP, Littler D, van Luenen H, Griffin PR, Wentworth P Jr, Borst P, Perrakis A Nucleic Acids Res. 2011 Mar 16. PMID:21415010^[2]

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

References

↑ Yu Z, Genest PA, ter Riet B, Sweeney K, DiPaolo C, Kieft R, Christodoulou E, Perrakis A, Simmons JM, Hausinger RP, van Luenen HG, Rigden DJ, Sabatini R, Borst P. The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase. Nucleic Acids Res. 2007;35(7):2107-15. Epub 2007 Mar 27. PMID:17389644 doi:http://dx.doi.org/10.1093/nar/gkm049
↑ Heidebrecht T, Christodoulou E, Chalmers MJ, Jan S, Ter Riet B, Grover RK, Joosten RP, Littler D, van Luenen H, Griffin PR, Wentworth P Jr, Borst P, Perrakis A. The structural basis for recognition of base J containing DNA by a novel DNA binding domain in JBP1. Nucleic Acids Res. 2011 Mar 16. PMID:21415010 doi:10.1093/nar/gkr125

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2xse"

@@ Line 3: / Line 3: @@
 <StructureSection load='2xse' size='340' side='right'caption='[[2xse]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xse]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Leita Leita]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XSE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XSE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xse]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leita Leita]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XSE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XSE FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymine_dioxygenase Thymine dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.6 1.14.11.6] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thymine_dioxygenase Thymine dioxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.6 1.14.11.6] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2xse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xse OCA], [http://pdbe.org/2xse PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xse RCSB], [http://www.ebi.ac.uk/pdbsum/2xse PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xse 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=2xse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xse OCA], [https://pdbe.org/2xse PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xse RCSB], [https://www.ebi.ac.uk/pdbsum/2xse PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xse ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/JBP1_LEITA JBP1_LEITA]] Dioxygenase that catalyzes the first step of DNA base J (beta-d-glucosyl-HOMedU) biosynthesis by converting thymine to 5-hydroxymethyluracil (HOMedU). DNA base J is a hypermodified thymidine residue found in the genome of kinetoplastid parasites, which is localized primarily to repetitive DNA, namely the telomeres, and is implicated in the regulation of antigenic variation. Also specifically binds to base J-containing DNA (J-DNA). Involved in propagation and maintenance of DNA base J synthesis initiated by JBP2 by specifically binding already synthesized DNA base J and propagating J synthesis. Thymine dioxygenase activity and J-DNA-binding are independent functions.<ref>PMID:17389644</ref>
+[[https://www.uniprot.org/uniprot/JBP1_LEITA JBP1_LEITA]] Dioxygenase that catalyzes the first step of DNA base J (beta-d-glucosyl-HOMedU) biosynthesis by converting thymine to 5-hydroxymethyluracil (HOMedU). DNA base J is a hypermodified thymidine residue found in the genome of kinetoplastid parasites, which is localized primarily to repetitive DNA, namely the telomeres, and is implicated in the regulation of antigenic variation. Also specifically binds to base J-containing DNA (J-DNA). Involved in propagation and maintenance of DNA base J synthesis initiated by JBP2 by specifically binding already synthesized DNA base J and propagating J synthesis. Thymine dioxygenase activity and J-DNA-binding are independent functions.<ref>PMID:17389644</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

2xse

From Proteopedia

Revision as of 12:16, 27 April 2022

The structural basis for recognition of J-base containing DNA by a novel DNA-binding domain in JBP1

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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