Da. Matthews et al., STRUCTURE OF HUMAN RHINOVIRUS 3C PROTEASE REVEALS A TRYPSIN-LIKE POLYPEPTIDE FOLD, RNA-BINDING SITE, AND MEANS FOR CLEAVING PRECURSOR POLYPROTEIN, Cell, 77(5), 1994, pp. 761-771
The structure of human rhinovirus-14 3C protease (3C(pro)) has been de
termined at 2.3 Angstrom resolution and refined to an R factor of 0.22
. This cysteine protease folds into two topologically equivalent six-s
tranded beta barrels and in this sense is similar to trypsin-like seri
ne proteases. However, there are differences in the lengths and positi
oning of individual beta strands as well as in loops connecting elemen
ts of secondary structure. The catalytic residues Cys-146, His-40, and
Glu-71 are positioned as in serine proteases, but the oxyanion hole i
s moved 1-1.2 Angstrom away. Residues that bind to the 5' noncoding re
gion of rhinovirus genomic RNA are located on the opposite side of the
molecule from the active site. Interactions between individual 3C(pro
) molecules in the crystal lattice suggest a model for intermolecular
proteolytic cleavage of the 3CD polyprotein.