 The
zinc metallopeptidase neurolysin is shown by x-ray crystallography
to have large structural elements erected over the active site region
that allow substrate access only through a deep narrow channel.
This architecture accounts for specialization of this neuropeptidase
to small bioactive peptide substrates without bulky secondary and
tertiary structures. In addition, modeling studies indicate that
the length of a substrate N-terminal to the site of hydrolysis is
restricted to approximately 10 residues by the limited size of the
active site cavity. Some structural elements of neurolysin, including
a five-stranded -sheet and the two active site helices, are conserved
with other metallopeptidases. The connecting loop regions of these
elements, however, are much extended in neurolysin, and they, together
with other open coil elements, line the active site cavity. These
potentially flexible elements may account for the ability of the
enzyme to cleave a variety of sequences. |
