title: Structural characterization of the isoenzymatic forms of human myeloperoxidase: evaluation of the iron-containing prosthetic group.
abstract: Myeloperoxidase (MPO) from human neutrophils has been purified and found to exist in three isoenzymatic forms, resolved by ion exchange chromatography. In addition to differences in subunit size and cellular compartmentalization of the isoenzymes, differences have been reported in their activity and susceptibility to inhibition. The structural basis of these isoenzymes is unclear; we attempted to further define their functional characteristics and structural identity. First, we measured respective enzymatic activity using a panel of substrates; MPO I was found to have lower activity with some substrates (pyrogallol, guaiacol, potassium iodide [KI]), but similar activity to the other isoenzymes with 4-aminoantipyrine. These studies confirm that MPO I is enzymatically distinct from MPO II and MPO III. Next, we examined the structural basis of these differences by evaluating the iron-containing prosthetic group in each form using electron paramagnetic resonance (EPR) and determination of the pyridine hemochrome. No significant difference between the isoenzymes was noted in these parameters, suggesting that the prosthetic group is the same in each protein. The cause for any difference in enzymatic activity must lie then in variations extrinsic to the heme, and based on previous studies of the gene and protein analysis, the posttranslational modification of MPO must account for these isoenzymatic species.
authors: William B. Castle Hematology Research Laboratory, Boston City Hospital, MA 02118.
authors: J
authors: J
authors: Wright
authors: N
authors: N
authors: Bastian
authors: T A
authors: TA
authors: Davis
authors: C
authors: C
authors: Zuo
authors: S
authors: S
authors: Yoshimoto
authors: W H
authors: WH
authors: Orme-Johnson
authors: A I
authors: AI
authors: Tauber
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D007501:Iron; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D009504:Neutrophils / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D007501:Iron; D009195:Peroxidase