Premium
Structural and mechanistic studies of peptidylglycine alpha‐amidating monooxygenase
Author(s) -
Amzel L. Mario,
Chufan Eduardo,
Rudzka Katarzyna,
Eipper Betty,
Mains Richard
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.195.3
Subject(s) - monooxygenase , chemistry , stereochemistry , biocatalysis , lyase , catalysis , enzyme , substrate (aquarium) , glycine , catalytic cycle , peptide , reaction mechanism , biochemistry , amino acid , cytochrome p450 , biology , ecology
Peptidylglycine α‐amidating monooxygenase (PAM) catalyzes the C‐terminal amidation of glycine‐extended peptides, a modification essential for the full activity of several peptide hormones and neurotransmitters. The amidation reaction is carried out sequentially by the two domains of PAM (peptidylglycine α‐hydroxylating monooxygenase (PHM) and peptidyl‐alpha‐hydroxyglycine alpha‐amidating lyase (PAL)). Investigating the structural and functional relations between the two domains as well as identifying the intermediates of the catalytic cycle is crucial to understating the catalytic reaction of PAM. Recently, the X‐ray structure of the isolated PAL domain was determined, complementing a series of X‐ray structures of PHM. The crystallographic studies of the catalytic cores, alone and in complex with substrate analogs and various small ligands, combined with mutational and kinetic studies provide insight into the mechanism of both catalytic steps. This work was supported by NSF grant MCB‐0450465 (L.M.A.) and NIH grant DK32949 (B.A.E. and R.E.M.)