Endothelin-converting enzyme (ECE) is a member of the zinc metalloprot
einase family. It is much more specific in its protease activity than
the bacterial metalloprotease thermolysin; we aim to construct a model
of its active site to help to explain these differences. We aligned t
he sequence of human ECE with those of human neprilysin (which is 39%
identical to ECE) and thermolysin. Residues believed to be important f
or inhibitor binding were assigned from the alignment and by analogy w
ith structural and functional studies of these enzymes. These included
a conserved IGG motif N-terminal to the zinc-binding HExxH motif, and
a tyrosine residue that may be analogous to Y157 of thermolysin. We h
ave used the program O to build a model of the active site of ECE base
d on the crystal structure of thermolysin.