Sorry if this point has become peripheral, but regarding thermodynamic
vs. kinetic control, I think the serpins are relevant:
murphy kenneth p (kpmurphy at blue.weeg.uiowa.edu) wrote:
: 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".
The serpin plasminogen activator inhibitor-1 becomes latent WITHOUT any
cleavage. The latent structure is similar to other cleaved serpin structures,
except that is it not cleaved. Prior to the conversion to latency, it is
in a conformation which is different, possibly flexible or mobile, which is
an inhibitory form. The only factors which influence the global minimum
in vivo will be complexation with ligands (e.g. vitronectin) or other environ-
mental factors. The protein in vitro shows kinetic control in that there
is a significant lifetime for the inhibitory state, before the irreversible
final folding to a more global minimum latent state. I don't know what the
current opinion is regarding the in vivo situation, where further factors
will influence both kinetics and thermodynamics.
