5TU6

PagF prenyltransferase with cyclic[INPYLYP] and DMSPP

Summary for 5TU6

• Entry DOI: 10.2210/pdb5tu6/pdb
• Related: 5TTY 5TU4 5TU5
• Descriptor: PagF prenyltransferase, cyclic[INPYLYP] peptide, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: ripp, prenylation, abba fold, transferase
• Biological source: Planktothrix agardhii NIES-596; More
• Total number of polymer chains: 2
• Total formula weight: 36563.96

Authors

Hao, Y.,Nair, S.K. (deposition date: 2016-11-04, release date: 2016-11-30, Last modification date: 2024-03-06)

Primary citation

Hao, Y.,Pierce, E.,Roe, D.,Morita, M.,McIntosh, J.A.,Agarwal, V.,Cheatham, T.E.,Schmidt, E.W.,Nair, S.K.
Molecular basis for the broad substrate selectivity of a peptide prenyltransferase.
Proc. Natl. Acad. Sci. U.S.A., 113:14037-14042, 2016

PubMed Abstract: The cyanobactin prenyltransferases catalyze a series of known or unprecedented reactions on millions of different substrates, with no easily observable recognition motif and exquisite regioselectivity. Here we define the basis of broad substrate tolerance for the otherwise uncharacterized TruF family. We determined the structures of the Tyr-prenylating enzyme PagF, in complex with an isoprenoid donor analog and a panel of linear and macrocyclic peptide substrates. Unexpectedly, the structures reveal a truncated barrel fold, wherein binding of large peptide substrates is necessary to complete a solvent-exposed hydrophobic pocket to form the catalytically competent active site. Kinetic, mutational, chemical, and computational analyses revealed the structural basis of selectivity, showing a small motif within peptide substrates that is sufficient for recognition by the enzyme. Attaching this 2-residue motif to two random peptides results in their isoprenylation by PagF, demonstrating utility as a general biocatalytic platform for modifications on any peptide substrate.

PubMed: 27872314
DOI: 10.1073/pnas.1609869113

Experimental method

X-RAY DIFFRACTION (2.22 Å)