2o3b: Difference between revisions

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[[Image:2o3b.gif|left|200px]]<br /><applet load="2o3b" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:2o3b.gif|left|200px]]<br /><applet load="2o3b" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2o3b, resolution 2.30Å" />

'''Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA'''<br />

==Overview==

Nonspecific, extracellular nucleases have received enhanced attention, recently as a consequence of the critical role that these enzymes can play, in infectivity by overcoming the host neutrophil defense system. The, activity of the cyanobacterial nuclease NucA, a member of the, betabetaalpha Me superfamily, is controlled by the specific nuclease, inhibitor, NuiA. Here we report the 2.3-A resolution crystal structure of, the NucA-NuiA complex, showing that NucA inhibition by NuiA involves an, unusual divalent metal ion bridge that connects the nuclease with its, inhibitor. The C-terminal Thr-135(NuiA) hydroxyl oxygen is directly, coordinated with the catalytic Mg(2+) of the nuclease active site, and, Glu-24(NuiA) also extends into the active site, mimicking the charge of a, scissile phosphate. NuiA residues Asp-75 and Trp-76 form a second, interaction site, contributing to the strength and specificity of the, interaction. The crystallographically defined interface is shown to be, consistent with results of studies using site-directed NuiA mutants. This, mode of inhibition differs dramatically from the exosite mechanism of, inhibition seen with the DNase colicins E7/E9 and from other, nuclease-inhibitor complexes that have been studied. The structure of this, complex provides valuable insights for the development of inhibitors for, related nonspecific nucleases that share the DRGH active site motif such, as the Streptococcus pneumoniae nuclease EndA, which mediates infectivity, of this pathogen, and mitochondrial EndoG, which is involved in, recombination and apoptosis.

Nonspecific, extracellular nucleases have received enhanced attention recently as a consequence of the critical role that these enzymes can play in infectivity by overcoming the host neutrophil defense system. The activity of the cyanobacterial nuclease NucA, a member of the betabetaalpha Me superfamily, is controlled by the specific nuclease inhibitor, NuiA. Here we report the 2.3-A resolution crystal structure of the NucA-NuiA complex, showing that NucA inhibition by NuiA involves an unusual divalent metal ion bridge that connects the nuclease with its inhibitor. The C-terminal Thr-135(NuiA) hydroxyl oxygen is directly coordinated with the catalytic Mg(2+) of the nuclease active site, and Glu-24(NuiA) also extends into the active site, mimicking the charge of a scissile phosphate. NuiA residues Asp-75 and Trp-76 form a second interaction site, contributing to the strength and specificity of the interaction. The crystallographically defined interface is shown to be consistent with results of studies using site-directed NuiA mutants. This mode of inhibition differs dramatically from the exosite mechanism of inhibition seen with the DNase colicins E7/E9 and from other nuclease-inhibitor complexes that have been studied. The structure of this complex provides valuable insights for the development of inhibitors for related nonspecific nucleases that share the DRGH active site motif such as the Streptococcus pneumoniae nuclease EndA, which mediates infectivity of this pathogen, and mitochondrial EndoG, which is involved in recombination and apoptosis.

==About this Structure==

2O3B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Anabaena_sp. Anabaena sp.] with NI, MG and MES as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2O3B OCA].

2O3B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Anabaena_sp. Anabaena sp.] with <scene name='pdbligand=NI:'>NI</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=MES:'>MES</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O3B OCA].

==Reference==

Line 14:

[[Category: Protein complex]]

[[Category: Ghosh, M.]]

[[Category: London, R.E.]]

[[Category: London, R E.]]

[[Category: Meiss, G.]]

[[Category: Pedersen, L.C.]]

[[Category: Pedersen, L C.]]

[[Category: Pingoud, A.M.]]

[[Category: Pingoud, A M.]]

[[Category: MES]]

[[Category: MG]]

Line 26:

[[Category: nuclease inhibitor]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:13:58 2008''

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@@ Line 1: / Line 1: @@
-[[Image:2o3b.gif|left|200px]]<br /><applet load="2o3b" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2o3b.gif|left|200px]]<br /><applet load="2o3b" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2o3b, resolution 2.30&Aring;" />
 '''Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA'''<br />
 ==Overview==
-Nonspecific, extracellular nucleases have received enhanced attention, recently as a consequence of the critical role that these enzymes can play, in infectivity by overcoming the host neutrophil defense system. The, activity of the cyanobacterial nuclease NucA, a member of the, betabetaalpha Me superfamily, is controlled by the specific nuclease, inhibitor, NuiA. Here we report the 2.3-A resolution crystal structure of, the NucA-NuiA complex, showing that NucA inhibition by NuiA involves an, unusual divalent metal ion bridge that connects the nuclease with its, inhibitor. The C-terminal Thr-135(NuiA) hydroxyl oxygen is directly, coordinated with the catalytic Mg(2+) of the nuclease active site, and, Glu-24(NuiA) also extends into the active site, mimicking the charge of a, scissile phosphate. NuiA residues Asp-75 and Trp-76 form a second, interaction site, contributing to the strength and specificity of the, interaction. The crystallographically defined interface is shown to be, consistent with results of studies using site-directed NuiA mutants. This, mode of inhibition differs dramatically from the exosite mechanism of, inhibition seen with the DNase colicins E7/E9 and from other, nuclease-inhibitor complexes that have been studied. The structure of this, complex provides valuable insights for the development of inhibitors for, related nonspecific nucleases that share the DRGH active site motif such, as the Streptococcus pneumoniae nuclease EndA, which mediates infectivity, of this pathogen, and mitochondrial EndoG, which is involved in, recombination and apoptosis.
+Nonspecific, extracellular nucleases have received enhanced attention recently as a consequence of the critical role that these enzymes can play in infectivity by overcoming the host neutrophil defense system. The activity of the cyanobacterial nuclease NucA, a member of the betabetaalpha Me superfamily, is controlled by the specific nuclease inhibitor, NuiA. Here we report the 2.3-A resolution crystal structure of the NucA-NuiA complex, showing that NucA inhibition by NuiA involves an unusual divalent metal ion bridge that connects the nuclease with its inhibitor. The C-terminal Thr-135(NuiA) hydroxyl oxygen is directly coordinated with the catalytic Mg(2+) of the nuclease active site, and Glu-24(NuiA) also extends into the active site, mimicking the charge of a scissile phosphate. NuiA residues Asp-75 and Trp-76 form a second interaction site, contributing to the strength and specificity of the interaction. The crystallographically defined interface is shown to be consistent with results of studies using site-directed NuiA mutants. This mode of inhibition differs dramatically from the exosite mechanism of inhibition seen with the DNase colicins E7/E9 and from other nuclease-inhibitor complexes that have been studied. The structure of this complex provides valuable insights for the development of inhibitors for related nonspecific nucleases that share the DRGH active site motif such as the Streptococcus pneumoniae nuclease EndA, which mediates infectivity of this pathogen, and mitochondrial EndoG, which is involved in recombination and apoptosis.
 ==About this Structure==
-O3B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Anabaena_sp. Anabaena sp.] with NI, MG and MES as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2O3B OCA].
+O3B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Anabaena_sp. Anabaena sp.] with <scene name='pdbligand=NI:'>NI</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=MES:'>MES</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O3B OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Protein complex]]
 [[Category: Ghosh, M.]]
-[[Category: London, R.E.]]
+[[Category: London, R E.]]
 [[Category: Meiss, G.]]
-[[Category: Pedersen, L.C.]]
+[[Category: Pedersen, L C.]]
-[[Category: Pingoud, A.M.]]
+[[Category: Pingoud, A M.]]
 [[Category: MES]]
 [[Category: MG]]
@@ Line 26: / Line 26: @@
 [[Category: nuclease inhibitor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 13:02:43 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:13:58 2008''