Rab Geranylgeranyltransferase - Reaction

Reaction

Rab geranylgeranyltransferase (RabGGTase; enzyme commission code EC 2.5.1.60) is classified as a transferase enzyme; specifically, it is in the protein prenyltransferase family along with two other enzymes (protein farnesyltransferase and protein geranylgeranyltransferase type-I). The reaction catalyzed by RabGGTase is summarized as follows:

  • geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate

This reaction is essential in the control of membrane docking and fusion. Studies of mice have shown that Rab GGTase genes are expressed in all major adult organs, as well as in some embryonic units, including the spinal cord and liver (Chinpaisal).

Rab geranylgeranyltransferase’s “outsourcing” of specificity (using REP to interact with the Rab proteins it prenylates, as mentioned above) is unique among prenyltransferases. Rab GGTase is “responsible for the largest number of individual protein prenylation events in the cell,” probably due to this ability to interact with many different Rab proteins (it can prenylate any sequence containing a cysteine residue).

In vitro studies have shown that Rab GGTase can be inhibited by nitrogen-containing bisphosphonate drugs such as risedronate; however, the effects of such drugs seem to be much more limited in vivo (Coxon).

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