Structural Basis of CDK4 Inhibition by p18ink4c

Abstract

Our research primarily revolves around the study of 1NK4 proteins. INN4 proteins are key regulators of cell cycle progression acting at the Gl-S phase transition. INK4 proteins act upstream of pRb tumor suppressor and thereby, control the expression of S-phase specific genes. We have determined the structure of p18INK4c to 1.95 A. We present the structure here and its implications for ankyrin repeat proteins and INN4 protein function. Based on the insight gained from our structure of p18INK4c, we have designed several mutants to study the impact of the mutation of specific residues on the efficacy of the INK4 proteins. We have determined that at least three mutants - F71N, F82Q, F92N have significantly higher thermostability than the wild-type protein. We present the 3D structures of these proteins as well as their efficacy in vivo in this report.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2001
Accession Number
ADA392269

Entities

People

  • Ravichandran N. Venkataramani
  • Ronen Marmorstein

Organizations

  • University of Pennsylvania

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biochemistry
  • Breast Cancer
  • Cell Physiological Processes
  • Chemical Stability
  • Chemical Synthesis
  • Chemistry
  • Crystal Structure
  • Free Energy
  • Hydrogen Bonds
  • Hydrophilic Properties
  • Hydrophobic Properties
  • Inhibition
  • Molecules
  • Protein-Protein Interactions
  • Thermostability
  • Transitions

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics