Related Experiment Video

Updated: Aug 19, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

The importance of dynamic effects on the enzyme activity: X-ray structure and molecular dynamics of onconase mutants

Antonello Merlino1, Lelio Mazzarella, Anna Carannante

  • 1Dipartimento di Chimica, Università degli Studi di Napoli "Federico II," Via Cynthia, 80126 Napoli, Italy.

The Journal of Biological Chemistry
|February 25, 2005
PubMed

Insights

Researchers studied Onconase (ONC) mutants to improve cancer chemotherapy. Structural analysis revealed insights into ONC

Area of Science:

  • Biochemistry
  • Structural Biology
  • Enzymology

Background:

  • Onconase (ONC), an RNase A superfamily member from Rana pipiens oocytes, exhibits anticancer properties.
  • Its therapeutic use is limited by low catalytic activity and significant renal toxicity, potentially linked to high thermal stability.

Purpose of the Study:

  • To investigate structural modifications in Onconase mutants (M23L-ONC and C87S,des103-104-ONC).
  • To elucidate the structural basis for altered activity and thermal stability in Onconase mutants.
  • To understand the molecular reasons for Onconase's lower catalytic efficiency and high stability compared to RNase A.

Main Methods:

  • X-ray crystallography to determine the structures of Onconase mutants.
  • Molecular dynamics simulations of Onconase and a specific mutant (C87S,des103-104-ONC).

Main Results:

  • Determined crystal structures of M23L-ONC and C87S,des103-104-ONC.
  • Molecular dynamics simulations provided insights into structural changes affecting enzyme properties.
  • Identified structural factors contributing to Onconase's low catalytic activity and high thermal stability.

Conclusions:

  • Structural insights into Onconase mutants can guide the development of improved anticancer agents.
  • Understanding Onconase's structure-function relationship is crucial for enhancing its therapeutic potential.
  • Mutant analysis provides a foundation for designing Onconase variants with reduced toxicity and increased efficacy.

More Related Videos

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis19:16

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis

Published on: March 17, 2010

Related Concept Videos

Introduction to Mechanisms of Enzyme Catalysis01:13

Introduction to Mechanisms of Enzyme Catalysis

For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild...
Enzymes02:34

Enzymes

Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Enzyme Kinetics01:19

Enzyme Kinetics

Enzymes speed up reactions by lowering the activation energy of the reactants. The speed at which the enzyme turns reactants into products is called the rate of reaction. Several factors impact the rate of reaction, including the number of available reactants. Enzyme kinetics is the study of how an enzyme changes the rate of a reaction.
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...