Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation.

ABSTRACT: N-terminal pyroglutamate (pGlu) formation from its glutaminyl (or glutamyl) precursor is required in the maturation of numerous bioactive peptides. The aberrant formation of pGlu may be related to several pathological processes, such as osteoporosis and amyloidotic diseases. This N-terminal cyclization reaction, once thought to proceed spontaneously, is greatly facilitated by the enzyme glutaminyl cyclase (QC). To probe this important but poorly understood modification, we present here the structure of human QC in free form and bound to a substrate and three imidazole-derived inhibitors. The structure reveals an alpha/beta scaffold akin to that of two-zinc exopeptidases but with several insertions and deletions, particularly in the active-site region. The relatively closed active site disp

SUBMITTER: Huang KF 

PROVIDER: S-EPMC1201592 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature