4X09

Structure of human RNase 6 in complex with sulphate anions

Summary for 4X09

• Entry DOI: 10.2210/pdb4x09/pdb
• Related: 2HKY
• Descriptor: Ribonuclease K6, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: rnase k6, hydrolase, pancreatic ribonuclease, rnase 7
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: Q93091
• Total number of polymer chains: 1
• Total formula weight: 15283.41

Authors

Prats-Ejarque, G.,Arranz-Trullen, J.,Blanco, J.A.,Pulido, D.,Moussaoui, M.,Boix, E. (deposition date: 2014-11-21, release date: 2016-04-06, Last modification date: 2024-10-23)

Primary citation

Prats-Ejarque, G.,Arranz-Trullen, J.,Blanco, J.A.,Pulido, D.,Nogues, M.V.,Moussaoui, M.,Boix, E.
The first crystal structure of human RNase 6 reveals a novel substrate-binding and cleavage site arrangement.
Biochem.J., 473:1523-1536, 2016

PubMed Abstract: Human RNase 6 is a cationic secreted protein that belongs to the RNase A superfamily. Its expression is induced in neutrophils and monocytes upon bacterial infection, suggesting a role in host defence. We present here the crystal structure of RNase 6 obtained at 1.72 Å (1 Å=0.1 nm) resolution, which is the first report for the protein 3D structure and thereby setting the basis for functional studies. The structure shows an overall kidney-shaped globular fold shared with the other known family members. Three sulfate anions bound to RNase 6 were found, interacting with residues at the main active site (His(15), His(122) and Gln(14)) and cationic surface-exposed residues (His(36), His(39), Arg(66) and His(67)). Kinetic characterization, together with prediction of protein-nucleotide complexes by molecular dynamics, was applied to analyse the RNase 6 substrate nitrogenous base and phosphate selectivity. Our results reveal that, although RNase 6 is a moderate catalyst in comparison with the pancreatic RNase type, its structure includes lineage-specific features that facilitate its activity towards polymeric nucleotide substrates. In particular, enzyme interactions at the substrate 5' end can provide an endonuclease-type cleavage pattern. Interestingly, the RNase 6 crystal structure revealed a novel secondary active site conformed by the His(36)-His(39) dyad that facilitates the polynucleotide substrate catalysis.

PubMed: 27013146
DOI: 10.1042/BCJ20160245

Experimental method

X-RAY DIFFRACTION (1.722 Å)