Huilin Li

Brookhaven National Laboratory, New York City, NY, United States

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Publications (5)42.19 Total impact

  • Source
    Dataset: Nettles.SOM
  • [Show abstract] [Hide abstract]
    ABSTRACT: The structure of epothilone A, bound to alpha,beta-tubulin in zinc-stabilized sheets, was determined by a combination of electron crystallography at 2.89 angstrom resolution and nuclear magnetic resonance-based conformational analysis. The complex explains both the broad-based epothilone structure-activity relationship and the known mutational resistance profile. Comparison with Taxol shows that the longstanding expectation of a common pharmacophore is not met, because each ligand exploits the tubulin-binding pocket in a unique and independent manner.
    Science 09/2004; 305(5685):866-9. · 31.20 Impact Factor
  • Microscopy and Microanalysis 07/2004; 10:1500 - 1501. · 2.50 Impact Factor
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    ABSTRACT: We have obtained a 3D reconstruction of intact microtubules, using cryoelectron microscopy and image processing, at a resolution of about 8 A, sufficient to resolve much of the secondary structure. The level of detail in the map allows docking of the tubulin structure previously determined by electron crystallography, with very strong constraints, providing several important insights not previously available through docking tubulin into lower-resolution maps. This work provides an improved picture of the interactions between adjacent protofilaments, which are responsible for microtubule stability, and also suggests that some structural features are different in microtubules from those in the zinc sheets with which the tubulin structure was determined.
    Structure 11/2002; 10(10):1317-28. · 5.99 Impact Factor
  • Kenneth H. Downing, Huilin Li
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    ABSTRACT: Many of the techniques that have been developed in X-ray crystallography are being applied in electron crystallographic studies of proteins. Electron crystallography has the advantage of measuring structure factor phases directly from high resolution images with an accuracy substantially higher than is common in X-ray crystallography. However, electron diffraction amplitudes are often not as precise as those obtained in X-ray work. We discuss here some approaches to maximizing the reliability of the diffraction amplitudes through choice of exposure and data processing schemes. With accurate measurement of diffraction data, Fourier difference methods can be used in electron crystallographic studies of small, localized changes of proteins that exist in two-dimensional crystals. The mathematical basis for the power of these methods in detecting small changes is reviewed. We then discuss several issues related to optimizing the quality of the diffraction data and derive an expression for the best exposure for recording diffraction patterns. An application of Fourier difference maps in localizing drug binding sites on the protein tubulin is discussed.
    Microscopy and Microanalysis 10/2001; 7(5):407-417. · 2.50 Impact Factor

Publication Stats

392 Citations
42.19 Total Impact Points

Institutions

  • 2004
    • Brookhaven National Laboratory
      • Biology Department
      New York City, NY, United States
    • Emory University
      • Department of Chemistry
      Atlanta, GA, United States
  • 2001–2002
    • Lawrence Berkeley National Laboratory
      • Life Sciences Division
      Berkeley, CA, United States