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 2.0  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.

Graphical abstractThe crystal structures of human type 2 methionine aminopeptidase complexed with l- and d-methionine were deduced by X-ray crystallography to establish the structural basis of enantiomer discrimination in natural substrates and inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide