Inhibitor Complexes of Ornithine Decarboxylase from Lactobacillus 30a Reveals a "Closed" State. Marcos Oliveira, Andrew Kern, Marvin L. Hackert. Department of Chemistry and Biochemistry University of Texas at Austin, Austin, TX, 78712.

Ornithine decarboxylase (OrnDC) controls a key step in the biosynthesis of polyamines, which in turn play a vital role in several cellular processes such as protein synthesis and DNA replication. Bacteria also have an inducible enzyme that has a pH optima of 5.8 and is thought to be involved in the regulation of cellular pH. The structure of OrnDC frm Lactobacillus 30a (OrnDC L30a) forms dodecamers, each monomer consisting of five domains. With data collected at CHESS the resolution has now been extended to 2.2A. The active site is found at the dimer interface on the bottom of a 27A deep channel. AGTP effector site has been characterized and its binding site has been localized on the surface of the enzyme at the entrance of the active site channel. It was speculated that GTP activates OrnDC L30a by stabilizing the closed state of the enzyme.

Two inhibitor compounds were studied Monofluoromethylornithine (MFMO) an irreversible inhibitor and 1,4diamino-2-butanonediamino (DAB). The MFMO complex shows the enzyme in a "closed" state and raises the possibility of asymmetry between active sites. The conformational changes are mostly restricted to the C-terminal domain that forms half of the active site channel. The largest conformational change (a 7A movement in the backbone structure) are localized in a small loop whose ends cover the active site and block the channel. The complex with DAB shows the pyridoxall-5'-phosphate cofactor in its external aldimine form and the inhibitor bound at the active site.