EC Number   |
General Information |
Reference |
|---|
   1.14.17.3 | malfunction |
disruption of AP-1-dependent late endosomal trafficking diminishes the ability of PAM to retain copper and produce amidated peptides. Impaired AP-1 function alters luminal copper delivery to PAM. Altered luminal cuproenzyme function may contribute to diseases associated with diminished AP-1 function. Reduced AP-1 function makes 18-kDa fragment amidation more sensitive to inhibition by bathocuproine disulfonate, a cell-impermeant Cu(I) chelator. The endocytic trafficking of PAM is altered, and PAM-1 accumulates on the cell surface when AP-1 levels are reduced |
745327 |
| 1.14.17.3 | malfunction |
mutating the His residues His364, His366, and His367 to Ala in the His-rich cluster (His-Gly-His-His) in the linker region connecting the enzyme's two catalytic domains affects enzyme trafficking. H3A mutation eliminates the ability of internalized PAM-1 to return to secretory granules |
745296 |
| 1.14.17.3 | malfunction |
the rs13175330 polymorphism of the PAM gene is selected from the ten single nucleotide polymorphisms (SNPs) most strongly associated with blood pressure. The presence of the G allele of the PAM rs13175330 A>G SNP is associated with a higher risk of hypertension after adjustments for age, sex, BMI, smoking, and drinking. The PAM rs13175330 A>G SNP is a candidate gene for hypertension in the Korean population. Additionally, the PAM rs13175330 G allele might be associated with insulin resistance and LDL atherogenicity in patients with hypertension. Phenotypes, overview |
745055 |
| 1.14.17.3 | metabolism |
copper metabolism is altered by PAM |
700421 |
| 1.14.17.3 | metabolism |
the enzyme catalyzes the final reaction in the maturation of alpha-amidated peptide hormones |
745459 |
| 1.14.17.3 | more |
solvent-exposed active site of enzyme PHM |
745298 |
| 1.14.17.3 | more |
structure of the PHM enzyme active site taken from PDB ID 1OPM structure with bound substrate diiodotyrosylglycine: the H-site coordinates to the Ndelta atom of H107, H108, and Nepsilon of H172, and the oxygen binding (catalytic) M-site coordinates to Nepsilon of H242 and H244 and the thiother S of M314. The side chain of the conserved E313 forms an H-bond to the main chain amide nitrogen of H244 |
744315 |
| 1.14.17.3 | more |
substrate binding triggers oxygen activation in peptidylglycine monooygenase |
744361 |
| 1.14.17.3 | more |
the protease-resistant catalytic core of PHM (PHMcc) is followed by a well conserved cluster of three His residues. This His cluster is included in the final exon encoding PHMcc and is followed by a poorly conserved, protease-sensitive region encoded by a short exon present in each of the major splice variants of PAM. The non-catalytic linker region between PHM and PAL includes a 315-nt exon in PAM-1. Exon 16 plays an important role in PAM-1 trafficking and in the ability of PAM-1 to participate in transmembrane signaling |
745296 |
| 1.14.17.3 | physiological function |
decreasing luminal pH is thought to play a role in the entry of newly synthesized and endocytosed membrane proteins into secretory granules. Secretory granule membrane proteins are retrieved and reused or degraded after exocytosis. The two catalytic domains of peptidylglycine alpha-amidating monooxygenase (PAM) catalyze the sequential reactions that convert peptidyl-Gly substrates into amidated products. A conserved His-rich cluster (His-Gly-His-His) in the linker region connecting its two catalytic domains senses pH and is involved in enzyme trafficking |
745296 |
