Molecular modeling of the active site of endothelin-converting enzyme.
Endothelin-converting enzyme (ECE) is a member of the zinc metalloproteinase 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 the sequence of human ECE with those of human neprilysin (which is 39% identical to ECE) and thermolysin. Residues believed to be important for inhibitor binding were assigned from the alignment and by analogy with 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 have used the program O to build a model of the active site of ECE based on the crystal structure of thermolysin.
Sansom
C E
CE
Department of Biochemistry and Molecular Biology, University of Leeds, England.
Hoang
V M
VM
Turner
A J
AJ
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry*; D001665:Binding Sites; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D008666:Metalloendopeptidases; D008958:Models, Molecular; D008969:Molecular Sequence Data
D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes