Methionine aminopeptidases and angiogenesis.
The initiator methionine residue of proteins is removed during synthesis by a specific and ubiquitous enzyme, methionine aminopeptidase (MetAP). Prokaryotes have a single gene, while eukaryotes have two isoforms. This family of metalloenzymes generally cleaves substrates in which the penultimate residue is one of the seven smaller amino acids (glycine, alanine, serine, threonine, proline, cysteine and valine). One of the eukaryotic isoforms (MetAP2) has an additional non-proteolytic function and is the principle target of a family of anti-angiogenic drugs that are related to fumagillin. The resulting covalent modification inhibits the protease activity of MetAP2 and blocks cell-cycle function in endothelial and some cancer cells. The role of MetAP2 in the mitogenic activity of these cells is unknown.
Bradshaw
Ralph A
RA
Department of Physiology and Biophysics, College of Medicine, University of California, Irvine, CA 92697, USA. rablab@uci.edu
Yi
Elizabeth
E
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry* / Q000502:physiology*; D000818:Animals; D006801:Humans; D063208:Methionyl Aminopeptidases; D008954:Models, Biological; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism; D009389:Neovascularization, Pathologic; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D020033:Protein Isoforms; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases