3FW0
Structure of Peptidyl-alpha-hydroxyglycine alpha-Amidating Lyase (PAL) bound to alpha-hydroxyhippuric acid (non-peptidic substrate)
Summary for 3FW0
| Entry DOI | 10.2210/pdb3fw0/pdb |
| Related | 3FVZ |
| Descriptor | Peptidyl-glycine alpha-amidating monooxygenase, MERCURY (II) ION, CALCIUM ION, ... (5 entities in total) |
| Functional Keywords | beta propeller, zinc, calcium, mercury, lyase, peptide amidation, substrate, hydroxyhippuric acid, alternative splicing, cleavage on pair of basic residues, copper, cytoplasmic vesicle, glycoprotein, membrane, metal-binding, monooxygenase, multifunctional enzyme, oxidoreductase, phosphoprotein, sulfation, transmembrane, vitamin c |
| Biological source | Rattus norvegicus (brown rat,rat,rats) |
| Cellular location | Cytoplasmic vesicle, secretory vesicle membrane; Single-pass membrane protein: P14925 |
| Total number of polymer chains | 1 |
| Total formula weight | 37550.52 |
| Authors | Chufan, E.E.,De, M.,Eipper, B.A.,Mains, R.E.,Amzel, L.M. (deposition date: 2009-01-16, release date: 2009-09-01, Last modification date: 2024-11-06) |
| Primary citation | Chufan, E.E.,De, M.,Eipper, B.A.,Mains, R.E.,Amzel, L.M. Amidation of bioactive peptides: the structure of the lyase domain of the amidating enzyme. Structure, 17:965-973, 2009 Cited by PubMed Abstract: Many neuropeptides and peptide hormones require amidation of their carboxy terminal for full biological activity. The enzyme peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL; EC 4.3.2.5) catalyzes the second and last step of this reaction, N-dealkylation of the peptidyl-alpha-hydroxyglycine to generate the alpha-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 alpha-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 alpha-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. PubMed: 19604476DOI: 10.1016/j.str.2009.05.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.52 Å) |
Structure validation
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