Figure 5.

Carboxylase turnover is limited by dissociation of propeptide-containing substrates. A, Short glutamate (Glu)-containing peptides [such as the pentapeptide Phe-Leu-Glu-Glu-Leu (FLEEL) shown] that lack a propeptide have binding affinity several orders of magnitude weaker than substrates with a linked propeptide. However, in the presence of high levels of short peptides, high rates of carboxylation are observed as the peptides quickly dissociate from the carboxylase after reaction. B, Substrates containing a propeptide (in gray) are tightly bound to the carboxylase at an exosite, and thus only slowly dissociate from the carboxylase. Uncarboxylated substrate is thus unable to access the carboxylase, reducing the overall rate of carboxylation. However, lengthy residency of substrates on the carboxylase could promote processivity, providing time to complete Glu carboxylation before dissociation. Gla, γ-carboxyglutamate.