2o3b
From Proteopedia
(New page: 200px<br /><applet load="2o3b" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o3b, resolution 2.30Å" /> '''Crystal structure co...) |
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| - | [[Image:2o3b.gif|left|200px]]<br /><applet load="2o3b" size=" | + | [[Image:2o3b.gif|left|200px]]<br /><applet load="2o3b" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2o3b, resolution 2.30Å" /> | caption="2o3b, resolution 2.30Å" /> | ||
'''Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA'''<br /> | '''Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Nonspecific, extracellular nucleases have received enhanced attention | + | 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== | ==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:// | + | 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== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Ghosh, M.]] | [[Category: Ghosh, M.]] | ||
| - | [[Category: London, R | + | [[Category: London, R E.]] |
[[Category: Meiss, G.]] | [[Category: Meiss, G.]] | ||
| - | [[Category: Pedersen, L | + | [[Category: Pedersen, L C.]] |
| - | [[Category: Pingoud, A | + | [[Category: Pingoud, A M.]] |
[[Category: MES]] | [[Category: MES]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: nuclease inhibitor]] | [[Category: nuclease inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:13:58 2008'' |
Revision as of 16:13, 21 February 2008
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Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA
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.
About this Structure
2O3B is a Protein complex structure of sequences from Anabaena sp. with , and as ligands. Full crystallographic information is available from OCA.
Reference
The nuclease a-inhibitor complex is characterized by a novel metal ion bridge., Ghosh M, Meiss G, Pingoud AM, London RE, Pedersen LC, J Biol Chem. 2007 Feb 23;282(8):5682-90. Epub 2006 Nov 30. PMID:17138564
Page seeded by OCA on Thu Feb 21 18:13:58 2008
Categories: Anabaena sp. | Protein complex | Ghosh, M. | London, R E. | Meiss, G. | Pedersen, L C. | Pingoud, A M. | MES | MG | NI | Metal complex | Non-specific nuclease | Nuclease | Nuclease inhibitor
