STRUCTURE OF THE ZINC ENDOPROTEASE FROM STREPTOMYCES-CAESPITOSUS

A zinc endoprotease produced by Streptomyces caespitosus (ScNP) specif ically hydrolyzes the peptide bond at the imino side of aromatic resid ues and is the smallest protease found to date. Although ScNP carries the zinc-binding sequence HEXXH, its primary structure of 132 amino ac id residues differs from those of other known zinc metalloendoprotease s, X-ray structural analysis of ScNP at 1.6 Angstrom resolution reveal ed that despite a lack of sequence homology, the common topological fe ature of main-chain folding and a beta-turn containing methionine, whi ch is a feature of the zinc metalloendoprotease superfamily of metzinc ins, is conserved in ScNP, The zinc atom of ScNP is tetrahedrally liga ted by the two histidines in the HEXXH sequence, an aspartate residue and a water molecule, Thus, ScNP represents a novel subfamily of metzi ncins with a HEXXHXXGXXD zinc-binding sequence. A plausible substrate recognition pocket to which aromatic residues bind is located near the catalytic zinc ion.