3fvz

Structure of Peptidyl-alpha-hydroxyglycine alpha-Amidating Lyase (PAL)

spinqualitylabelsall models 3fvz, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3fvz is a 1 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CA, FE, GOL, ZN Related: 3fw0, 1phm Gene: Pam (Buffalo rat) Activity: Peptidylamidoglycolate lyase, with EC number 4.3.2.5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [AMD_RAT] Bifunctional enzyme that catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides. The monooxygenase part produces an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated to glyoxylate and the corresponding desglycine peptide amide by the lyase part. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Amidation of bioactive peptides: the structure of the lyase domain of the amidating enzyme.,Chufan EE, De M, Eipper BA, Mains RE, Amzel LM Structure. 2009 Jul 15;17(7):965-73. PMID:19604476 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monooxygenase

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