Structural highlights
Publication Abstract from PubMed
Enzymes that form nitrogen-nitrogen bonds are employed in natural product biosynthesis and the nitrogen cycle. Piperazate synthase forms the cyclic hydrazine l-piperazic acid from l-N(5)-OH-ornithine, using heme as a cofactor. In this work, we discover sequence-related enzyme NohD that instead reacts with l-N(5)-OH-ornithine to release ammonia, and we solve its structure to 1.4 A resolution. We then employ structure-guided site-directed mutagenesis to endow variants of NohD with piperazate synthase activity. Crystal structures of the NohD variants reveal how the heme propionate changes conformation, positioning it upward toward the amino nitrogen, where it is likely to activate the amine for N-N bond-formation. This study highlights a key structural requirement for N-N bond-formation and sets the stage for the development of new N-N-bond-forming catalysts.
Conversion of a Heme-Dependent Dehydratase to a Piperazate Synthase Reveals the Role of the Heme Propionate Group in N-N Bond-Formation.,Higgins MA, Mirotadze N, Shi X, Hoffarth ER, Du YL, Ryan KS J Am Chem Soc. 2025 Oct 29;147(43):39160-39168. doi: 10.1021/jacs.5c08886. Epub , 2025 Oct 16. PMID:41101755[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Higgins MA, Mirotadze N, Shi X, Hoffarth ER, Du YL, Ryan KS. Conversion of a Heme-Dependent Dehydratase to a Piperazate Synthase Reveals the Role of the Heme Propionate Group in N-N Bond-Formation. J Am Chem Soc. 2025 Oct 29;147(43):39160-39168. PMID:41101755 doi:10.1021/jacs.5c08886
