6pd1

From Proteopedia

PntC-AEPT: fusion protein of phosphonate-specific cytidylyltransferase and 2-aminoethylphosphonate (AEP) transaminase from Treponema denticola

Structural highlights

6pd1 is a 4 chain structure with sequence from Treponema denticola ATCC 35405. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.72Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PNTCW_TREDE Bifunctional transferase involved in the biosynthesis of cell-surface phosphonates (PubMed:31420548). The aminotransferase region catalyzes the transformation of phosphonoacetaldehyde (PnAA) to 2-aminoethylphosphonate (AEP) (PubMed:31420548). The cytidylyltransferase region catalyzes the activation of 2-aminoethylphosphonate (AEP) to CMP-2-aminoethylphosphonate (CMP-AEP) (PubMed:31420548). Cannot use phosphocholine (PubMed:31420548). Exhibits strong activity towards CTP, limited activity towards ATP and no activity with GTP (PubMed:31420548).^[1]

Publication Abstract from PubMed

Phosphonates are rare and unusually bioactive natural products. However, most bacterial phosphonate biosynthetic capacity is dedicated to tailoring cell surfaces with molecules like 2-aminoethylphosphonate (AEP). Although phosphoenolpyruvate mutase (Ppm)-catalyzed installation of C-P bonds is known, subsequent phosphonyl tailoring (Pnt) pathway steps remain enigmatic. Here we identify nucleotidyltransferases in over two-thirds of phosphonate biosynthetic gene clusters, including direct fusions to ~60% of Ppm enzymes. We characterize two putative phosphonyl tailoring cytidylyltransferases (PntCs) that prefer AEP over phosphocholine (P-Cho) - a similar substrate used by the related enzyme LicC, which is a virulence factor in Streptococcus pneumoniae. PntC structural analyses reveal steric discrimination against phosphocholine. These findings highlight nucleotidyl activation as a predominant chemical logic in phosphonate biosynthesis and set the stage for probing diverse phosphonyl tailoring pathways.

The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis.,Rice K, Batul K, Whiteside J, Kelso J, Papinski M, Schmidt E, Pratasouskaya A, Wang D, Sullivan R, Bartlett C, Weadge JT, Van der Kamp MW, Moreno-Hagelsieb G, Suits MD, Horsman GP Nat Commun. 2019 Aug 16;10(1):3698. doi: 10.1038/s41467-019-11627-6. PMID:31420548^[2]

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

References

↑ Rice K, Batul K, Whiteside J, Kelso J, Papinski M, Schmidt E, Pratasouskaya A, Wang D, Sullivan R, Bartlett C, Weadge JT, Van der Kamp MW, Moreno-Hagelsieb G, Suits MD, Horsman GP. The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis. Nat Commun. 2019 Aug 16;10(1):3698. doi: 10.1038/s41467-019-11627-6. PMID:31420548 doi:http://dx.doi.org/10.1038/s41467-019-11627-6
↑ Rice K, Batul K, Whiteside J, Kelso J, Papinski M, Schmidt E, Pratasouskaya A, Wang D, Sullivan R, Bartlett C, Weadge JT, Van der Kamp MW, Moreno-Hagelsieb G, Suits MD, Horsman GP. The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis. Nat Commun. 2019 Aug 16;10(1):3698. doi: 10.1038/s41467-019-11627-6. PMID:31420548 doi:http://dx.doi.org/10.1038/s41467-019-11627-6