1vs0

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[[Image:1vs0.gif|left|200px]]
 
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==Crystal Structure of the Ligase Domain from M. tuberculosis LigD at 2.4A==
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The line below this paragraph, containing "STRUCTURE_1vs0", creates the "Structure Box" on the page.
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<StructureSection load='1vs0' size='340' side='right'caption='[[1vs0]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1vs0]] 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=1VS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VS0 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APK:5-O-[(S)-{[(5S)-5-AMINO-6-OXOHEXYL]AMINO}(HYDROXY)PHOSPHORYL]ADENOSINE'>APK</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_1vs0| PDB=1vs0 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1vs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vs0 OCA], [https://pdbe.org/1vs0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vs0 RCSB], [https://www.ebi.ac.uk/pdbsum/1vs0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vs0 ProSAT]</span></td></tr>
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</table>
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'''Crystal Structure of the Ligase Domain from M. tuberculosis LigD at 2.4A'''
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== Function ==
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[https://www.uniprot.org/uniprot/LIGD_MYCTU LIGD_MYCTU] With Ku forms a non-homologous end joining (NHEJ) repair enzyme which repairs DNA double-strand breaks (DSB) with reduced fidelity. Recognizes, processes and reseals DSBs, including repairs on incompatible DSB which require 3'-resection, gap filling and ligation. Anneals the 3' overhanging strands from opposing breaks to form a gapped intermediate, which then can be extended in trans by using the termini as primers for extension of the annealed break. Binds to the recessed 5'-phosphate moiety of the downstream DNA strand forming a stable synaptic complex even when the 3'-protruding ends of the template DNA strands are not complementary. Has numerous activities; gap filling copies the template strand, and prefers a 5'-phosphate in the gap and rNTPS (PubMed:17174332, PubMed:17947582), DNA-directed DNA or RNA polymerase on 5'-overhangs, terminal transferase (extending ssDNA or blunt dsDNA in a non-templated fashion, preferentially with rNTPs), DNA-dependent RNA primase (synthesizes short RNAs on unprimed closed ssDNA) and 3'- to 5'-exonuclease on ssDNA (PubMed:15499016). Isolated Pol domain (and presumably the holoenzyme) is able to form complexes between 2 noncompatible protruding 3'-ends DNA ends via microhomologous DNA strands, in a end-bridging function to which it adds a templated nucleotide (PubMed:17947582). Minimal primer length is 2 nucleotides (PubMed:21255731).<ref>PMID:15499016</ref> <ref>PMID:17174332</ref> <ref>PMID:17947582</ref> <ref>PMID:21255731</ref> The preference of the polymerase domain for rNTPs over dNTPs may be advantageous in dormant cells, where the dNTP pool is limiting. In conjunction with endogenous or Mycobacterium phage Omega Ku (AC Q853W0) can reconstitute NHEJ in Saccharomyces cerevisiae.
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== Evolutionary Conservation ==
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==Overview==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vs/1vs0_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1vs0 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
DNA ligase D (LigD) is a large polyfunctional enzyme involved in nonhomologous end-joining (NHEJ) in mycobacteria. LigD consists of a C-terminal ATP-dependent ligase domain fused to upstream polymerase and phosphoesterase modules. Here we report the 2.4 angstroms crystal structure of the ligase domain of Mycobacterium LigD, captured as the covalent ligase-AMP intermediate with a divalent metal in the active site. A chloride anion on the protein surface coordinated by the ribose 3'-OH and caged by arginine and lysine side chains is a putative mimetic of the 5'-phosphate at a DNA nick. Structure-guided mutational analysis revealed distinct requirements for the adenylylation and end-sealing reactions catalyzed by LigD. We found that a mutation of Mycobacterium LigD that ablates only ligase activity results in decreased fidelity of NHEJ in vivo and a strong bias of mutagenic events toward deletions instead of insertions at the sealed DNA ends. This phenotype contrasts with the increased fidelity of double-strand break repair in deltaligD cells or in a strain in which only the polymerase function of LigD is defective. We surmise that the signature error-prone quality of bacterial NHEJ in vivo arises from a dynamic balance between the end-remodeling and end-sealing steps.
DNA ligase D (LigD) is a large polyfunctional enzyme involved in nonhomologous end-joining (NHEJ) in mycobacteria. LigD consists of a C-terminal ATP-dependent ligase domain fused to upstream polymerase and phosphoesterase modules. Here we report the 2.4 angstroms crystal structure of the ligase domain of Mycobacterium LigD, captured as the covalent ligase-AMP intermediate with a divalent metal in the active site. A chloride anion on the protein surface coordinated by the ribose 3'-OH and caged by arginine and lysine side chains is a putative mimetic of the 5'-phosphate at a DNA nick. Structure-guided mutational analysis revealed distinct requirements for the adenylylation and end-sealing reactions catalyzed by LigD. We found that a mutation of Mycobacterium LigD that ablates only ligase activity results in decreased fidelity of NHEJ in vivo and a strong bias of mutagenic events toward deletions instead of insertions at the sealed DNA ends. This phenotype contrasts with the increased fidelity of double-strand break repair in deltaligD cells or in a strain in which only the polymerase function of LigD is defective. We surmise that the signature error-prone quality of bacterial NHEJ in vivo arises from a dynamic balance between the end-remodeling and end-sealing steps.
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==About this Structure==
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Crystal structure and nonhomologous end-joining function of the ligase component of Mycobacterium DNA ligase D.,Akey D, Martins A, Aniukwu J, Glickman MS, Shuman S, Berger JM J Biol Chem. 2006 May 12;281(19):13412-23. Epub 2006 Feb 13. PMID:16476729<ref>PMID:16476729</ref>
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1VS0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VS0 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal structure and nonhomologous end-joining function of the ligase component of Mycobacterium DNA ligase D., Akey D, Martins A, Aniukwu J, Glickman MS, Shuman S, Berger JM, J Biol Chem. 2006 May 12;281(19):13412-23. Epub 2006 Feb 13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16476729 16476729]
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</div>
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[[Category: Mycobacterium tuberculosis]]
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<div class="pdbe-citations 1vs0" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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== References ==
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[[Category: Akey, D.]]
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<references/>
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[[Category: Aniukwu, J.]]
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__TOC__
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[[Category: Berger, J M.]]
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</StructureSection>
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[[Category: Glickman, M S.]]
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[[Category: Large Structures]]
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[[Category: Martins, A.]]
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[[Category: Mycobacterium tuberculosis H37Rv]]
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[[Category: Shuman, S.]]
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[[Category: Akey D]]
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[[Category: TBSGC, TB Structural Genomics Consortium.]]
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[[Category: Aniukwu J]]
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[[Category: Ligase]]
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[[Category: Berger JM]]
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[[Category: Nucleotidyl transferase]]
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[[Category: Glickman MS]]
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[[Category: Ob fold]]
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[[Category: Martins A]]
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[[Category: Protein structure initiative]]
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[[Category: Shuman S]]
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[[Category: Psi]]
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[[Category: Structural genomic]]
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[[Category: Tb structural genomics consortium]]
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[[Category: Tbsgc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:51:19 2008''
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Current revision

Crystal Structure of the Ligase Domain from M. tuberculosis LigD at 2.4A

PDB ID 1vs0

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