Journal
STRUCTURE
Volume 17, Issue 7, Pages 965-973Publisher
CELL PRESS
DOI: 10.1016/j.str.2009.05.008
Keywords
-
Funding
- U.S. Department of Energy
- Office of Science
- Office of Basic Energy Sciences [DE-AC02-06CH11357]
- National Science Foundation [MCB-0450465]
- National Institutes of Health [DK32949]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [0920288] Funding Source: National Science Foundation
Ask authors/readers for more resources
Many neuropeptides and peptide hormones require amidation of their carboxy terminal for full biological activity. The enzyme peptidyl-a-hydroxyglycine a-amidating lyase (PAL; EC 4.3.2.5) catalyzes the second and last step of this reaction, N-dealkylation of the peptidyl-a-hydroxyglycine to generate the a-amidated peptide and glyoxylate. Here we report the X-ray crystal structure of the PAL catalytic core (PALcc) alone and in complex with the nonpeptidic substrate a-hydroxyhippuric acid. The structures show that PAL folds as a six-bladed beta-propeller. The active site is formed by a Zn(II) ion coordinated by three histidine residues; the substrate binds to this site with its a-hydroxyl group coordinated to the Zn(II) ion. The structures also reveal a tyrosine residue (Tyr(654)) at the active site as the catalytic base for hydroxyl deprotonation, an unusual role for tyrosine. A reaction mechanism is proposed based on this structural data and validated by biochemical analysis of site-directed PALcc mutants.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available