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Related Experiment Videos

Crystallization of human thymidylate synthase.

C A Schiffer1, V J Davisson, D V Santi

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.

Journal of Molecular Biology
|May 20, 1991
PubMed
Summary

Researchers crystallized human thymidylate synthase without ligands, achieving diffraction beyond 3.0 A. This structural study provides a foundation for understanding enzyme function and developing targeted therapies.

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Crystallography

Background:

  • Human thymidylate synthase is a critical enzyme in DNA synthesis.
  • Understanding its structure is key to developing antifolate drugs.
  • Previous structural studies may have been limited by ligand presence.

Purpose of the Study:

  • To crystallize human thymidylate synthase in a ligand-free state.
  • To determine the crystal structure and unit cell dimensions.
  • To provide a structural basis for future drug development.

Main Methods:

  • Cloning and expression of human thymidylate synthase in Escherichia coli.
  • Crystallization using ammonium sulfate, beta-mercaptoethanol, and varying pH.
  • X-ray diffraction analysis to determine crystal properties.

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Main Results:

  • Successfully crystallized ligand-free human thymidylate synthase.
  • Crystals diffract beyond 3.0 A resolution.
  • Trigonal space group P3(1)21 with unit cell dimensions a = b = 96.7 A, c = 84.1 A.

Conclusions:

  • The ligand-free crystal form of human thymidylate synthase is suitable for high-resolution structural analysis.
  • This provides a crucial structural template for rational drug design.
  • Further studies can explore ligand binding and inhibition mechanisms.