1b6a
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HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470
OverviewOverview
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.
About this StructureAbout this Structure
1B6A is a Single protein structure of sequence from Homo sapiens with CO and TN4 as ligands. Active as Methionyl aminopeptidase, with EC number 3.4.11.18 Full crystallographic information is available from OCA.
ReferenceReference
Structure of human methionine aminopeptidase-2 complexed with fumagillin., Liu S, Widom J, Kemp CW, Crews CM, Clardy J, Science. 1998 Nov 13;282(5392):1324-7. PMID:9812898
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