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CRM1 (also known as XPO1 and exportin 1) mediates nuclear export of hundreds of proteins through the recognition of the leucine-rich nuclear export signal (LR-NES). Here we present the 2.9 Å structure of CRM1 bound to snurportin 1 (SNUPN). Snurportin 1 binds CRM1 in a bipartite manner by means of an amino-terminal LR-NES and its nucleotide-binding domain. The LR-NES is a combined α-helical-extended structure that occupies a hydrophobic groove between two CRM1 outer helices. The LR-NES interface explains the consensus hydrophobic pattern, preference for intervening electronegative residues and inhibition by leptomycin B. The second nuclear export signal epitope is a basic surface on the snurportin 1 nucleotide-binding domain, which binds an acidic patch on CRM1 adjacent to the LR-NES site. Multipartite recognition of individually weak nuclear export signal epitopes may be common to CRM1 substrates, enhancing CRM1 binding beyond the generally low affinity LR-NES. Similar energetic construction is also used in multipartite nuclear localization signals to provide broad substrate specificity and rapid evolution in nuclear transport., Nuclear localization and export signals (NLSs and NESS) are recognized by karyopherin-β (Kap-β, also known as importin and exportin) proteins to direct macromolecules in and out of the nucleus (1-4). [...]

Ornithine decarboxylase (ODC) is an obligate homodimer that catalyzes the pyridoxal 5'-phosphate-dependent decarboxylation of L-ornithine to putrescine in polyamine biosynthesis. It is reported that ODC is investigated as a therapeutic target for a number of proliferative diseases and has proved to be an effective target in the treatment of African sleeping sickness, a fatal tropical disease.

The mutation of retinoid X receptor (RXR) and identification of an orthogonal ligand-receptor pair are described. The compounds activate mutant receptors effectively and hence it is shown that the inactive 'near drugs' developed during research programs are a reservoir of chemical potential that can be exploited in conjunction with mutant proteins that possess altered specificities.

Results support that long-range energetic coupling of interface residues to the active site is necessary for ornithine decarboxylase function. Further, the catalytic function of the enzyme is governed by the enzyme's dimer interface, enabling access by small molecules to the enzyme interface without energy barriers.

Results show that formation of putrescine by ornithine decarboxylase is dependent on the alpha-carbon protonation as indicated by the mutation of cysteine-360 residue of the enzyme to alanine or serine. The rate-limiting step in the enzyme steady-state reaction involves Schiff base hydrolysis.