protein folding

Simon Brocklehurst Bioc smb18 at mole.bio.cam.ac.uk
Tue Apr 19 08:56:53 EST 1994


engh at nmrvex.biochem.mpg.de (Richard Engh) writes:

>X-Newsreader: TIN [version 1.1 PL8]

>Regarding differences between nmr, X-ray, and
>physiological structures:

(Points 1 and 2 deleted)

>3)  To some extent, the very high agreement in general between X-ray
>and NMR structures may be influenced by the fact that rigid proteins
>crystallize better than flexible ones; so the comparisons deal mostly
>with rigid proteins.  There has been a lot of attention given to  the
>serpin family of proteinase inhibitors lately; these must be flexible
>for their activity.  A literature search with "serpin" as...
    
It's might be worth remembering when thinking about this particular point that
both X-ray crystallography and multidimensional NMR spectroscopy provide
time-averaged models (with some qualitative information about flexibility).
If time-averaged models are not appropriate descriptions of the structure
(e.g. because the proteins, or bits of the proteins are "flexible") then 
we shouldn't expect the two techniques to produce "results" that are
in agreement.
  The point, though, is that when we have characterised the structure of a
protein, protein-protein complex, protein-nucleic acid complex etc in a 
VARIETY of different environments e.g. solution + crystal, and the results are
IN AGREEMENT, then surely we can bet that we have a good model for the
"physiological" structure.
   It's not realistic (or even always possible) to do this for every case,
so we need to be able to extraopolate...

Thus, at the moment it seems that X-ray structures of isolated globular
proteins are likely to be pretty useful models, as are X-ray models of high
affinity protein - "other molecule" complexes.  The jury is still out on
how useful crystallography by itself will be for weakly associating
systems.

!-----------------------------------------------------------------------
Simon M. Brocklehurst
Cambridge Centre for Molecular Recognition
Department of Biochemistry
University of Cambridge
Cambridge
UK

E-mail: s.m.brocklehurst at bioc.cam.ac.uk




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