A conserved carboxy-terminal RxG motif in the NgBR subunit of cis-prenyltransferase is critical for prenyltransferase activity [Lipids]

cis-Prenyltransferases (cisPTs) constitute a large family of enzymes conserved during evolution and present in all domains of life. In eukaryotes and archaea, cisPT is the first enzyme committed to the synthesis of dolichyl phosphate (DolP), an obligate lipid carrier in protein glycosylation reactions. The homodimeric bacterial enzyme, undecaprenyl diphosphate synthase (UPPS), generates 11 isoprene units and has been structurally and mechanistically characterized in great detail. Recently, we discovered that unlike UPPS, mammalian cisPT is a heteromer consisting of NgBR (NUS1) and hCIT (DHDDS) subunits, and this composition has been confirmed in plants and fungal cisPTs. Here, we establish the first purification system for heteromeric cisPT and show that both NgBR and hCIT subunits function in catalysis and substrate binding. Finally, we identified a critical RxG sequence in the C-terminal tail of NgBR that is conserved and essential for enzyme activity across phyla. In summary, our findings show that eukaryotic cisPT is composed of the NgBR and hCIT subunits. The strong conservation of the RxG motif amongst NgBR orthologs implicates this subunit in the synthesis of polyprenol diphosphates critical for cellular function.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2xulnP6
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