2o3b

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{{STRUCTURE_2o3b| PDB=2o3b | SCENE= }}
{{STRUCTURE_2o3b| PDB=2o3b | SCENE= }}
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'''Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA'''
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===Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17138564 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17138564}}
==About this Structure==
==About this Structure==
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[[Category: Nuclease]]
[[Category: Nuclease]]
[[Category: Nuclease inhibitor]]
[[Category: Nuclease inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:16:25 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:54:50 2008''

Revision as of 09:54, 28 July 2008

Template:STRUCTURE 2o3b

Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA

Template:ABSTRACT PUBMED 17138564

About this Structure

2O3B is a Protein complex structure of sequences from Anabaena sp.. 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

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