Department of Biochemistry, Duke University School of Medicine
This year’s ASBMB annual meeting was held in San Diego between April 2 – 6. Ken was invited to give a talk about our recent progress in the Moco project. He also chaired a session for structure studies of complex systems in Bioinorganic Catalysis. The program is available online.
In the recent review article in the Current Opinion in Chemical Biology by Guenter Schwarz, our MoaC structure paper (PNAS 2015) was referenced and highlighted as an article of outstanding interest. This review paper nicely summarizes the current status of the research in Moco biosynthesis and human Moco deficiency disease. The author referenced four of our original research publication with the PNAS 2015 paper as the work that settled the discussion about the functions of MoaA and MoaC.
Each year, ~4 students receive poster awards during our department retreat. This year, Abhi received a poster award, joining our previous recipients; Edward (2014 retreat) and Brad (2011 and 2013 retreat). So far, we have a record of four-straight years!! (note: we did not have retreat in 2012)
This paper describes successful entrapment of previously uncharacterized reaction intermediate of MoaC reaction using an uncleavable substrate analog, 3′,8-cH2GTP. Intriguingly, the trapped intermediate was tightly bound to MoaC, likely through covalent modification, making the analog as the first mechanism-based inhibitor of bacterial Moco biosynthesis. The results revealed that the unique tetracyclic structure of cPMP (MoaC product) was constructed via a concerted formation of pterin and cyclic phosphate rings, which is distinct from previously proposed stepwise mechanism. Brad found the irreversible inhibition and performed most of the basic characterization, and Edward performed some nice follow up experiments including the MS characterization of the inhibited MoaC.
