PDBsum entry 4peq

Hydrolase/hydrolase inhibitor

PDB id: 4peq

Contents

Protein chains

124 a.a.

453 a.a.

Waters ×562

PDB id:

4peq

Name:

Hydrolase/hydrolase inhibitor

Title:

Structure of bovine ribonuclease inhibitor complexed with bovine ribonuclease i

Structure:

Ribonuclease pancreatic. Chain: a, c. Fragment: unp residues 27-150. Synonym: rnase 1,rnase a. Engineered: yes. Ribonuclease/angiogenin inhibitor 1. Chain: b, d. Engineered: yes

Source:

Bos taurus. Bovine. Organism_taxid: 9913. Gene: rnase1, rns1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: rnh1.

Resolution:

2.21Å R-factor: 0.177 R-free: 0.226

Authors:

C.M.Bianchetti,J.E.Lomax,R.T.Raines,B.G.Fox

Key ref:

J.E.Lomax et al. (2014). Functional evolution of ribonuclease inhibitor: insights from birds and reptiles. J Mol Biol, 426, 3041-3056. PubMed id: 24941155 DOI: 10.1016/j.jmb.2014.06.007

Date:

24-Apr-14 Release date: 25-Jun-14

Protein chains

P61823  (RNAS1_BOVIN) -  Ribonuclease pancreatic from Bos taurus

Seq: 150 a.a.

Struc: 124 a.a.

Protein chains

Q3SZN8  (Q3SZN8_BOVIN) -  Ribonuclease inhibitor from Bos taurus

Seq: 456 a.a.

Struc: 453 a.a.

Enzyme reactions

• Enzyme class: Chains A, C: E.C.4.6.1.18 - pancreatic ribonuclease.
• Reaction:
  1. an [RNA] containing cytidine + H2O = an [RNA]-3'-cytidine- 3'-phosphate + a 5'-hydroxy-ribonucleotide-3'-[RNA]
  2. an [RNA] containing uridine + H2O = an [RNA]-3'-uridine-3'-phosphate + a 5'-hydroxy-ribonucleotide-3'-[RNA]

DOI no: 10.1016/j.jmb.2014.06.007

J Mol Biol 426:3041-3056 (2014)

PubMed id: 24941155

Functional evolution of ribonuclease inhibitor: insights from birds and reptiles.

J.E.Lomax, C.M.Bianchetti, A.Chang, G.N.Phillips, B.G.Fox, R.T.Raines.

ABSTRACT

Ribonuclease inhibitor (RI) is a conserved protein of the mammalian cytosol. RI binds with high affinity to diverse secretory ribonucleases (RNases) and inhibits their enzymatic activity. Although secretory RNases are found in all vertebrates, the existence of a non-mammalian RI has been uncertain. Here, we report on the identification and characterization of RI homologs from chicken and anole lizard. These proteins bind to RNases from multiple species but exhibit much greater affinity for their cognate RNases than for mammalian RNases. To reveal the basis for this differential affinity, we determined the crystal structure of mouse, bovine, and chicken RI·RNase complexes to a resolution of 2.20, 2.21, and 1.92Å, respectively. A combination of structural, computational, and bioinformatic analyses enabled the identification of two residues that appear to contribute to the differential affinity for RNases. We also found marked differences in oxidative instability between mammalian and non-mammalian RIs, indicating evolution toward greater oxygen sensitivity in RIs from mammalian species. Taken together, our results illuminate the structural and functional evolution of RI, along with its dynamic role in vertebrate biology.