1b59
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The fungal metabolite fumagillin suppresses the formation of new blood | + | 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 Structure== | ==About this Structure== | ||
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[[Category: Methionyl aminopeptidase]] | [[Category: Methionyl aminopeptidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Clardy, J | + | [[Category: Clardy, J C.]] |
[[Category: Liu, S.]] | [[Category: Liu, S.]] | ||
[[Category: CO]] | [[Category: CO]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:51:42 2008'' |
Revision as of 09:51, 21 February 2008
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COMPLEX OF HUMAN METHIONINE AMINOPEPTIDASE-2 COMPLEXED WITH OVALICIN
Overview
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 Structure
1B59 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Methionyl aminopeptidase, with EC number 3.4.11.18 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 11:51:42 2008
