6PD2

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

Summary for 6PD2

• Entry DOI: 10.2210/pdb6pd2/pdb
• Descriptor: Nucleotidyl transferase/aminotransferase, class V, PYRIDOXAL-5'-PHOSPHATE, MAGNESIUM ION, ... (9 entities in total)
• Functional Keywords: phosphonate, cytidylyltransferase, cytidine monophosphate- 2-aminoethylphosphonate (cmp-aep), biosynthetic protein
• Biological source: Treponema denticola (strain ATCC 35405 / CIP 103919 / DSM 14222)
• Total number of polymer chains: 4
• Total formula weight: 286580.54

Authors

Suits, M.D.L.,Whiteside, J. (deposition date: 2019-06-18, release date: 2019-08-07, Last modification date: 2023-10-11)

Primary citation

Rice, K.,Batul, K.,Whiteside, J.,Kelso, J.,Papinski, M.,Schmidt, E.,Pratasouskaya, A.,Wang, D.,Sullivan, R.,Bartlett, C.,Weadge, J.T.,Van der Kamp, M.W.,Moreno-Hagelsieb, G.,Suits, M.D.,Horsman, G.P.
The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis.
Nat Commun, 10:3698-3698, 2019

PubMed Abstract: 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.

PubMed: 31420548
DOI: 10.1038/s41467-019-11627-6

Experimental method

X-RAY DIFFRACTION (1.95 Å)