This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


6cq2

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:29, 13 March 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 1: Line 1:
==Crystal structure of Mycobacterium tuberculosis Topoisomerase I in complex with oligonucleotide MTS2-12 and Magnesium==
==Crystal structure of Mycobacterium tuberculosis Topoisomerase I in complex with oligonucleotide MTS2-12 and Magnesium==
-
<StructureSection load='6cq2' size='340' side='right' caption='[[6cq2]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+
<StructureSection load='6cq2' size='340' side='right'caption='[[6cq2]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[6cq2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CQ2 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[6cq2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CQ2 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 3.004&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5d5h|5d5h]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">topA, Rv3646c, MTCY15C10.06 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=6cq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cq2 OCA], [https://pdbe.org/6cq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cq2 RCSB], [https://www.ebi.ac.uk/pdbsum/6cq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cq2 ProSAT]</span></td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase DNA topoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.2 5.99.1.2] </span></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=6cq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cq2 OCA], [http://pdbe.org/6cq2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cq2 RCSB], [http://www.ebi.ac.uk/pdbsum/6cq2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cq2 ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/TOP1_MYCTU TOP1_MYCTU]] Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone.[HAMAP-Rule:MF_00952]<ref>PMID:20724443</ref> The C-terminus (residues 622-934) inhibits RNA cleavage by MazF4.<ref>PMID:20724443</ref>
+
[https://www.uniprot.org/uniprot/TOP1_MYCTU TOP1_MYCTU] Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone.[HAMAP-Rule:MF_00952]<ref>PMID:20724443</ref> The C-terminus (residues 622-934) inhibits RNA cleavage by MazF4.<ref>PMID:20724443</ref>
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
We have obtained new crystal structures of Mycobacterium tuberculosis topoisomerase I, including structures with ssDNA substrate bound to the active site, with and without Mg2+ ion present. Significant enzyme conformational changes upon DNA binding place the catalytic tyrosine in a pre-transition state position for cleavage of a specific phosphodiester linkage. Meanwhile, the enzyme/DNA complex with bound Mg2+ ion may represent the post-transition state for religation in the enzyme's multiple-step DNA relaxation catalytic cycle. The first observation of Mg2+ ion coordinated with the TOPRIM residues and DNA phosphate in a type IA topoisomerase active site allows assignment of likely catalytic role for the metal and draws a comparison to the proposed mechanism for type IIA topoisomerases. The critical function of a strictly conserved glutamic acid in the DNA cleavage step was assessed through site-directed mutagenesis. The functions assigned to the observed Mg2+ ion can account for the metal requirement for DNA rejoining but not DNA cleavage by type IA topoisomerases. This work provides new structural insights into a more stringent requirement for DNA rejoining versus cleavage in the catalytic cycle of this essential enzyme, and further establishes the potential for selective interference of DNA rejoining by this validated TB drug target.
+
-
 
+
-
Investigating mycobacterial topoisomerase I mechanism from the analysis of metal and DNA substrate interactions at the active site.,Cao N, Tan K, Annamalai T, Joachimiak A, Tse-Dinh YC Nucleic Acids Res. 2018 Jun 14. pii: 5037723. doi: 10.1093/nar/gky492. PMID:29905859<ref>PMID:29905859</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 6cq2" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==
-
*[[Topoisomerase|Topoisomerase]]
+
*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: DNA topoisomerase]]
+
[[Category: Large Structures]]
-
[[Category: Myctu]]
+
[[Category: Mycobacterium tuberculosis H37Rv]]
-
[[Category: Cao, N]]
+
[[Category: Cao N]]
-
[[Category: Tan, K]]
+
[[Category: Tan K]]
-
[[Category: Thirunavukkaraus, A]]
+
[[Category: Thirunavukkaraus A]]
-
[[Category: Tse-Dinh, Y C]]
+
[[Category: Tse-Dinh Y-C]]
-
[[Category: Co-crystallization]]
+
-
[[Category: Complex with oligonucleotide and magnesium]]
+
-
[[Category: Isomerase]]
+
-
[[Category: Isomerase-dna complex]]
+
-
[[Category: Mycobacterium tuberculosis]]
+
-
[[Category: Topoisomerase i]]
+

Current revision

Crystal structure of Mycobacterium tuberculosis Topoisomerase I in complex with oligonucleotide MTS2-12 and Magnesium

PDB ID 6cq2

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6cq2"
Personal tools