1B6A

HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470

Summary for 1B6A

• Entry DOI: 10.2210/pdb1b6a/pdb
• Descriptor: METHIONINE AMINOPEPTIDASE, COBALT (II) ION, (1R,2S,3S,4R)-4-hydroxy-2-methoxy-4-methyl-3-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]cyclohexyl (chloroacetyl)carbamate, ... (4 entities in total)
• Functional Keywords: angiogenesis inhibitor, aminopeptidase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 53493.29

Authors

Liu, S.,Clardy, J.C. (deposition date: 1999-01-13, release date: 2000-01-13, Last modification date: 2024-10-23)

Primary citation

Liu, S.,Widom, J.,Kemp, C.W.,Crews, C.M.,Clardy, J.
Structure of human methionine aminopeptidase-2 complexed with fumagillin.
Science, 282:1324-1327, 1998

PubMed Abstract: The fungal metabolite fumagillin suppresses the formation of new blood vessels, and a fumagillin analog is currently in clinical trials as an anticancer agent. The molecular target of fumagillin is methionine aminopeptidase-2 (MetAP-2). A 1.8 A resolution crystal structure of free and inhibited human MetAP-2 shows a covalent bond formed between a reactive epoxide of fumagillin and histidine-231 in the active site of MetAP-2. Extensive hydrophobic and water-mediated polar interactions with other parts of fumagillin provide additional affinity. Fumagillin-based drugs inhibit MetAP-2 but not MetAP-1, and the three-dimensional structure also indicates the likely determinants of this specificity. The structural basis for fumagillin's potency and specificity forms the starting point for structure-based drug design.

PubMed: 9812898
DOI: 10.1126/science.282.5392.1324

Experimental method

X-RAY DIFFRACTION (1.6 Å)