Using structure to elucidate function mechanism
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Using Structure to Elucidate Function/Mechanism. An experimental strategy for. determining the arrangement of atoms/molecules in space to obtain structural information. Some situations in which this strategy might be applied. understand a mechanism in detail

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An experimental strategy for

  • determining the arrangement of atoms/molecules in space to obtain structural information

Some situations in which this strategy might be applied

  • understand a mechanism in detail

  • structure-based (rational) drug design

  • elucidate a novel structure

  • understand a conformational switch (e.g. prions)

Some methods that provide structural information:

  • X ray bombardment of crystals

  • circular dichroism (CD)

  • nuclear magnetic resonance (NMR)- size < 25 kD

  • sequence comparison/analysis (e.g. COILS or threading)- surface residues are most conserved

  • electron microscopy (EM)

  • atomic force microscopy

  • photo/chemical cross-linking

  • protease digestion

  • calorimetry

  • sedimentation

Circular Dichroism

The differential absorption of radiation polarized in two directions as a function of frequency is called dichroism.Circular dichroism (CD) spectroscopy is a form of light absorption spectroscopy that measures the difference in absorbance of right- and left-circularly polarized light (rather than the commonly used absorbance of isotropic light) by a substance.

Kurt D. Berndt

Circular Dichroism

Circular dichroism is very sensitive to the secondary structure of polypeptides and proteins.

Kurt D. Berndt

What are the experimental prerequisites for structural studies?

  • material for study should be of homogeneous composition. How?

  • often useful to reduce the complexity of the problem by focusing on a subregion of a larger molecule. How?

  • minimize flexibility of the molecule in solution so that only a small number of conformations are possible. How?

What are possible pitfalls of crystallographic studies? studies?

  • biologically irrelevant structure? Less common than you might think.

  • faulty interpretation. Interfaces that form during packing of molecules into a crystal may not be biologically relevant. Solution?