ยท
R.S. Bhatnagar,K. Futterer,T.A. Farazi, S. Korolev,C.L. Murray, E.
Jackson-Machelski, G.W. Gokel, J.I. Gordon, and G. Waksman.
Structure of N-myristoyltransferase with bound myristoylCoA and peptide
substrate analogs
Nature Structural Biology. 5:1091-1097. (1998)
N-myristoyltransferase (Nmt) attaches
myristate to the N-terminal glycine of many important eukaryotic and viral
proteins. It is a target for anti- fungal and anti-viral therapy. We have
determined the structure, at 2.9 A resolution, of a ternary complex of
Saccharomyces cerevisiae Nmt1p with bound myristoylCoA and peptide substrate
analogs. The model reveals structural features that define the enzyme's
substrate specificities and regulate the ordered binding and release of
substrates and products. A novel catalytic mechanism is proposed involving
deprotonation of the N-terminal ammonium of a peptide substrate by the enzyme's
C-terminal backbone carboxylate.