Human methionine aminopeptidase type 2 in complex with L- and D-methionine.
Human methionine aminopeptidase type 2 (hMetAP-2) was identified as the molecular target of anti-angiogenic agents such as fumagillin and its analogues. We describe here the crystal structure of hMetAP-2 in complex with l-methionine and d-methionine at 1.9 and 2.0A resolution, respectively. The comparison of the structure of the two complexes establishes the basis of enantiomer discrimination and provides some considerations for the design of selective MetAP-2 inhibitors.
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853-1301, USA.
M Cristina
MC
Nonato
Joanne
J
Widom
Jon
J
Clardy
D000626:Aminopeptidases / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism; D008715:Methionine / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation
D008715:Methionine; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases