Human glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site.

ABSTRACT:

Background

Glutaminyl cyclase (QC) forms the pyroglutamyl residue at the amino terminus of numerous secretory peptides and proteins. We previously proposed the mammalian QC has some features in common with zinc aminopeptidases. We now have generated a structural model for human QC based on the aminopeptidase fold (pdb code 1AMP) and mutated the apparent active site residues to assess their role in QC catalysis.

Results

The structural model proposed here for human QC, deposited in the protein databank as 1MOI, is supported by a variety of fold prediction programs, by the circular dichroism spectrum, and by the presence of the disulfide. Mutagenesis of the six active site residues present in both 1AMP and QC reveal essential roles for the two histidines (140 and 330, QC number

SUBMITTER: Booth RE 

PROVIDER: S-EPMC368447 | biostudies-literature | 2004 Feb

REPOSITORIES: biostudies-literature