2o3b

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spinqualitylabelsall models 2o3b, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 NI, MG and MES 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

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