1tae: Difference between revisions

Revision as of 16:11, 21 February 2008

Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal

OverviewOverview

DNA ligase is an enzyme important for DNA repair and replication. Eukaryotic genomes encode ligases requiring ATP as the cofactor; bacterial genomes encode NAD(+)-dependent ligase. This difference in substrate specificities and the essentiality of NAD(+)-dependent ligase for bacterial survival make NAD(+)-dependent ligase a good target for designing highly specific anti-infectives. Any such structure-guided effort would require the knowledge of the precise mechanism of NAD+ recognition by the enzyme. We report the principles of NAD+ recognition by presenting the synthesis of NAD+ from nicotinamide mononucleotide (NMN) and AMP, catalyzed by Enterococcus faecalis ligase within the crystal lattice. Unprecedented conformational change, required to reorient the two subdomains of the protein for the condensation to occur and to recognize NAD+, is captured in two structures obtained using the same protein crystal. Structural data and sequence analysis presented here confirms and extends prior functional studies of the ligase adenylation reaction.

About this StructureAbout this Structure

1TAE is a Single protein structure of sequence from Enterococcus faecalis v583 with , and as ligands. Active as DNA ligase (NAD(+)), with EC number 6.5.1.2 Full crystallographic information is available from OCA.

ReferenceReference

Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal., Gajiwala KS, Pinko C, Structure. 2004 Aug;12(8):1449-59. PMID:15296738

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OCA

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-[[Image:1tae.gif|left|200px]]<br /><applet load="1tae" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1tae.gif|left|200px]]<br /><applet load="1tae" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1tae, resolution 2.70&Aring;" />
 '''Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal'''<br />
 ==Overview==
-DNA ligase is an enzyme important for DNA repair and replication., Eukaryotic genomes encode ligases requiring ATP as the cofactor; bacterial, genomes encode NAD(+)-dependent ligase. This difference in substrate, specificities and the essentiality of NAD(+)-dependent ligase for, bacterial survival make NAD(+)-dependent ligase a good target for, designing highly specific anti-infectives. Any such structure-guided, effort would require the knowledge of the precise mechanism of NAD+, recognition by the enzyme. We report the principles of NAD+ recognition by, presenting the synthesis of NAD+ from nicotinamide mononucleotide (NMN), and AMP, catalyzed by Enterococcus faecalis ligase within the crystal, lattice. Unprecedented conformational change, required to reorient the two, subdomains of the protein for the condensation to occur and to recognize, NAD+, is captured in two structures obtained using the same protein, crystal. Structural data and sequence analysis presented here confirms and, extends prior functional studies of the ligase adenylation reaction.
+DNA ligase is an enzyme important for DNA repair and replication. Eukaryotic genomes encode ligases requiring ATP as the cofactor; bacterial genomes encode NAD(+)-dependent ligase. This difference in substrate specificities and the essentiality of NAD(+)-dependent ligase for bacterial survival make NAD(+)-dependent ligase a good target for designing highly specific anti-infectives. Any such structure-guided effort would require the knowledge of the precise mechanism of NAD+ recognition by the enzyme. We report the principles of NAD+ recognition by presenting the synthesis of NAD+ from nicotinamide mononucleotide (NMN) and AMP, catalyzed by Enterococcus faecalis ligase within the crystal lattice. Unprecedented conformational change, required to reorient the two subdomains of the protein for the condensation to occur and to recognize NAD+, is captured in two structures obtained using the same protein crystal. Structural data and sequence analysis presented here confirms and extends prior functional studies of the ligase adenylation reaction.
 ==About this Structure==
-TAE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecalis_v583 Enterococcus faecalis v583] with SO4, NA and NAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA_ligase_(NAD(+)) DNA ligase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.5.1.2 6.5.1.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TAE OCA].
+TAE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecalis_v583 Enterococcus faecalis v583] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA_ligase_(NAD(+)) DNA ligase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.5.1.2 6.5.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TAE OCA].
 ==Reference==
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 [[Category: Enterococcus faecalis v583]]
 [[Category: Single protein]]
-[[Category: Gajiwala, K.S.]]
+[[Category: Gajiwala, K S.]]
 [[Category: Pinko, C.]]
 [[Category: NA]]
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 [[Category: nucleotidyl transferase fold]]
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