7cpn

Publication Abstract from PubMed

cis-Prenyltransferases (cis-PTs) catalyze consecutive condensations of isopentenyl diphosphate to an allylic diphosphate acceptor to produce a linear polyprenyl diphosphate of designated length. Dimer formation is a prerequisite for cis-PTs to catalyze all cis-prenyl condensation reactions. The structure-function relationship of a conserved C-terminal RXG motif in cis-PTs that forms inter-subunit interactions and has a role in catalytic activity has attracted much attention. Here, we solved the crystal structure of a medium-chain cis-PT from Thermobifida fusca that produces dodecaprenyl diphosphate as a polyprenoid glycan carrier for cell wall synthesis. The structure revealed a characteristic dimeric architecture of cis-PTs in which a rigidified RXG motif of one monomer formed inter-subunit hydrogen bonds with the catalytic site of the other monomer, while the RXG motif of the latter remained flexible. Careful analyses suggested the existence of a possible long-range negative cooperativity between the two catalytic sites on the two monomeric subunits that allowed the binding of one subunit to stabilize the formation of the enzyme-substrate ternary complex and facilitated the release of Mg-PPi and subsequent intra-molecular translocation at the counter subunit so that the condensation reaction could occur in consecutive cycles. The current structure reveals the dynamic nature of the RXG motif and provides a rationale for pursuing further investigations to elucidate the inter-subunit cooperativity of cis-PTs.

Crystal structure of Thermobifida fusca cis-prenyltransferase reveals the dynamic nature of its RXG motif-mediated inter-subunit interactions critical for its catalytic activity.,Kurokawa H, Ambo T, Takahashi S, Koyama T Biochem Biophys Res Commun. 2020 Nov 12;532(3):459-465. doi:, 10.1016/j.bbrc.2020.08.062. Epub 2020 Sep 4. PMID:32892948^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.