In article <2vgd4iINN23mt at sat.ipp-garching.mpg.de>,
Richard Engh <engh at nmrvex.biochem.mpg.de> wrote:
>This very interesting fundamental discussion is a little bit
>disguised by the rather more specific subject title...
>>Regarding thermodynamic versus kinetic control of protein
>folding, I would like to mention the case of some serpin
>protein inhibitors, in particular plasminogen activator
>inhibitor, studied by E. Goldsmith and co-workers.
>PAI has an inhibitory fold in vitro only for
>a limited time, and then undergoes a transition to a latent
>state (see Mottonen et al., Nature 355, 270-273, 1992; see
>also a recent issue of Structure for related
>serpin work and discussion).
>>In vivo, the active form may be stabilized by complexation.
>The point is, the primary functional conformation is NOT
>the global minimum for the isolated protein. Is this
>kinetic control? Even if the complexed form in vivo IS
>a global minimum (and I don't know what the current opinion
>on this is), is it a case where a metastable fold has to be
>'captured' and complexed.
>>Any serpin researchers reading this who could comment?
>>-R.Engh
But isn't there a cleavage involved in obtaining the "latent" state? This
really difines a new system and it's entirely possible that the global minimum
is differen in this new system. I really don't see the serpin example as
directly addressing the issue of thermodynamic vs kinetic "control".
Kip
--
Dr. Kenneth P. Murphy e-mail: k-murphy at uiowa.edu
Department of Biochemistry office: (319)335-8910
Univeristy of Iowa lab: (319)335-7936
Iowa City, IA 52242 FAX: (319)335-9570
