3sma

Publication Abstract from PubMed

The enzyme FrbF has attracted significant attention due to its role in The enzyme FrbF from Streptomyces rubellomurinus has attracted significant attention due to its role in the biosynthesis of the antimalarial phosphonate FR-900098. The enzyme catalyzes acetyl transfer onto the hydroxamate of the FR-900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine 5'-monophosphate-N-hydroxy-3-aminopropylphosphonate. In spite of the established function as a bona fide N-acetyltransferase, FrbF shows no sequence similarity with any member of the GCN5-like N-acetyltransferase (GNAT) superfamily. Here, we present the 2.0 A resolution crystal structure of FrbF in complex with acetyl-CoA that demonstrates a unique architecture that is distinct from those of canonical GNAT-like acetyltransferases. We also utilize the co-crystal structure to guide structure-function studies that identify the roles of putative active site residues in the acetyltransferase mechanism. The combined biochemical and structural analyses of FrbF provide insights into this previously uncharacterized family of N-acetyltransferases and also provides a molecular framework towards the production of novel N-acyl derivatives of FR-900098.

A new N-acetyltransferase fold in the structure and mechanism of the phosphonate biosynthetic enzyme FrbF.,Bae B, Cobb R, Desieno MA, Zhao H, Nair SK J Biol Chem. 2011 Aug 24. PMID:21865168^[1]

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