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6krh

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Current revision

Structural basis for domain rotation during adenylation of active site K123 and fragment library screening against NAD+ -dependent DNA ligase from Mycobacterium tuberculosis

Structural highlights

6krh is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DNLJ_MYCTU DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA.[HAMAP-Rule:MF_01588]

Publication Abstract from PubMed

NAD(+)-dependent DNA ligase (LigA) is the principal bacterial ligase and catalyses a multistep ligation reaction. The adenylation (AdD) domain at the N-terminus consists of subdomains 1a and 1b, where subdomain 1a is unique to LigA. Small-angle X-ray scattering and X-ray diffraction studies were used to probe changes in the relative spatial dispositions of the two subdomains during the adenylation reaction. Structural analyses of the inter-subdomain interactions of the AdD domain suggest that salt bridges formed by Glu22, Glu26 and Glu87 of subdomain 1a with Arg144, Arg315 and His240 of subdomain 1b play an important role in stabilizing the intermediate conformations of the two subdomains. E22A, E26A and E87A mutations reduce the in vitro activity by 89%, 64% and 39%, respectively, on a nicked DNA substrate, while they show no activity loss on a pre-adenylated DNA substrate, thus suggesting that the salt bridges are important in the initial steps of the ligation reaction. Furthermore, the E22A, E26A and E87A mutants exhibited extremely delayed growth in complementation assays involving the Escherichia coli GR501 strain, which harbours its own temperature-sensitive LigA. The H236A and H236Y mutants, which involve the residue that stacks against the adenine moiety of AMP, severely impact the activity and the ability to complement the growth-defective E. coli GR501 strain. Analysis of the K123A and K123R mutations in the active site rationalizes their total loss of activity and inability to rescue the growth-defective E. coli GR501 strain.

Salt bridges at the subdomain interfaces of the adenylation domain and active-site residues of Mycobacterium tuberculosis NAD(+)-dependent DNA ligase A (MtbLigA) are important for the initial steps of nick-sealing activity.,Afsar M, Shukla A, Kumar N, Ramachandran R Acta Crystallogr D Struct Biol. 2021 Jun 1;77(Pt 6):776-789. doi:, 10.1107/S2059798321003107. Epub 2021 May 14. PMID:34076591^[1]

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

References

↑ Afsar M, Shukla A, Kumar N, Ramachandran R. Salt bridges at the subdomain interfaces of the adenylation domain and active-site residues of Mycobacterium tuberculosis NAD(+)-dependent DNA ligase A (MtbLigA) are important for the initial steps of nick-sealing activity. Acta Crystallogr D Struct Biol. 2021 Jun 1;77(Pt 6):776-789. doi:, 10.1107/S2059798321003107. Epub 2021 May 14. PMID:34076591 doi:http://dx.doi.org/10.1107/S2059798321003107

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6krh"

Categories: Large Structures | Mycobacterium tuberculosis H37Rv | Afsar M | Ramachandran R | Shukla A

@@ Line 3: / Line 3: @@
 <StructureSection load='6krh' size='340' side='right'caption='[[6krh]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6krh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KRH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6krh]] is a 1 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=6KRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KRH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.6&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ligA, lig, Rv3014c, MTV012.28c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA_ligase_(NAD(+)) DNA ligase (NAD(+))], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.5.1.2 6.5.1.2] </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=6krh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6krh OCA], [https://pdbe.org/6krh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6krh RCSB], [https://www.ebi.ac.uk/pdbsum/6krh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6krh ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/DNLJ_MYCTU DNLJ_MYCTU]] DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA.[HAMAP-Rule:MF_01588]
+[https://www.uniprot.org/uniprot/DNLJ_MYCTU DNLJ_MYCTU] DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA.[HAMAP-Rule:MF_01588]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 19: @@
 </div>
 <div class="pdbe-citations 6krh" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA ligase 3D structures|DNA ligase 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Afsar, M]]
+[[Category: Afsar M]]
-[[Category: Ramachandran, R]]
+[[Category: Ramachandran R]]
-[[Category: Shukla, A]]
+[[Category: Shukla A]]
-[[Category: Ligase]]

6krh

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Current revision

Structural basis for domain rotation during adenylation of active site K123 and fragment library screening against NAD+ -dependent DNA ligase from Mycobacterium tuberculosis

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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