PDBsum entry 1ymw

Hydrolase

PDB id: 1ymw

Contents

Protein chain

124 a.a. *

Waters ×144

* Residue conservation analysis

PDB id:

1ymw

Name:

Hydrolase

Title:

The study of reductive unfolding pathways of rnase a (y92g mutant)

Structure:

Ribonuclease pancreatic. Chain: a. Synonym: rnase 1, rnase a. Engineered: yes. Mutation: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Gene: rnase1, rns1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.50Å R-factor: 0.216 R-free: 0.244

Authors:

G.Xu,M.Narayan,I.Kurinov,D.R.Ripoll,E.Welker,M.Khalili,S.E.Ealick, H.A.Scheraga

Key ref:

G.Xu et al. (2006). A localized specific interaction alters the unfolding pathways of structural homologues. J Am Chem Soc, 128, 1204-1213. PubMed id: 16433537 DOI: 10.1021/ja055313e

Date:

21-Jan-05 Release date: 31-Jan-06

Protein chain

P61823  (RNAS1_BOVIN) -  Ribonuclease pancreatic from Bos taurus

Seq: 150 a.a.

Struc: 124 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: 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: 10.1021/ja055313e

J Am Chem Soc 128:1204-1213 (2006)

PubMed id: 16433537

A localized specific interaction alters the unfolding pathways of structural homologues.

G.Xu, M.Narayan, I.Kurinov, D.R.Ripoll, E.Welker, M.Khalili, S.E.Ealick, H.A.Scheraga.

ABSTRACT

Reductive unfolding studies of proteins are designed to provide information about intramolecular interactions that govern the formation (and stabilization) of the native state and about folding/unfolding pathways. By mutating Tyr92 to G, A, or L in the model protein, bovine pancreatic ribonuclease A, and through analysis of temperature factors and molecular dynamics simulations of the crystal structures of these mutants, it is demonstrated that the markedly different reductive unfolding rates and pathways of ribonuclease A and its structural homologue onconase can be attributed to a single, localized, ring-stacking interaction between Tyr92 and Pro93 in the bovine variant. The fortuitous location of this specific stabilizing interaction in a disulfide-bond-containing loop region of ribonuclease A results in the localized modulation of protein dynamics that, in turn, enhances the susceptibility of the disulfide bond to reduction leading to an alteration in the reductive unfolding behavior of the homologues. These results have important implications for folding studies involving topological determinants to obtain folding/unfolding rates and pathways, for protein structure-function prediction through fold recognition, and for predicting proteolytic cleavage sites.