7CPM

CRYSTAL STRUCTURE OF DODECAPRENYL DIPHOSPHATE SYNTHASE FROM THERMOBIFIDA FUSCA

Summary for 7CPM

• Entry DOI: 10.2210/pdb7cpm/pdb
• Descriptor: Trans,polycis-polyprenyl diphosphate synthase ((2Z,6E)-farnesyl diphosphate specific) (2 entities in total)
• Functional Keywords: prenyltransferase, transferase
• Biological source: Thermobifida fusca (strain YX)
• Total number of polymer chains: 6
• Total formula weight: 195874.77

Authors

Kurokawa, H.,Ambo, T.,Takahashi, S.,Koyama, T. (deposition date: 2020-08-07, release date: 2020-10-14, Last modification date: 2023-11-29)

Primary citation

Kurokawa, H.,Ambo, T.,Takahashi, S.,Koyama, T.
Crystal structure of Thermobifida fusca cis-prenyltransferase reveals the dynamic nature of its RXG motif-mediated inter-subunit interactions critical for its catalytic activity.
Biochem.Biophys.Res.Commun., 532:459-465, 2020

PubMed Abstract: 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.

PubMed: 32892948
DOI: 10.1016/j.bbrc.2020.08.062

Experimental method

X-RAY DIFFRACTION (2.6 Å)