1qzy
From Proteopedia
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==Overview== | ==Overview== | ||
| - | LAF389 is a synthetic analogue of bengamides, a class of marine natural | + | LAF389 is a synthetic analogue of bengamides, a class of marine natural products that produce inhibitory effects on tumor growth in vitro and in vivo. A proteomics-based approach has been used to identify signaling pathways affected by bengamides. LAF389 treatment of cells resulted in altered mobility of a subset of proteins on two-dimensional gel electrophoresis. Detailed analysis of one of the proteins, 14-3-3gamma, showed that bengamide treatment resulted in retention of the amino-terminal methionine, suggesting that bengamides directly or indirectly inhibited methionine aminopeptidases (MetAps). Both known MetAps are inhibited by LAF389. Short interfering RNA suppression of MetAp2 also altered amino-terminal processing of 14-3-3gamma. A high resolution structure of human MetAp2 co-crystallized with a bengamide shows that the compound binds in a manner that mimics peptide substrates. Additionally, the structure reveals that three key hydroxyl groups on the inhibitor coordinate the di-cobalt center in the enzyme active site. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Methionyl aminopeptidase]] | [[Category: Methionyl aminopeptidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Eck, M | + | [[Category: Eck, M J.]] |
[[Category: Morollo, A.]] | [[Category: Morollo, A.]] | ||
| - | [[Category: Song, H | + | [[Category: Song, H K.]] |
[[Category: CO]] | [[Category: CO]] | ||
[[Category: TBU]] | [[Category: TBU]] | ||
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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 14:45:36 2008'' |
Revision as of 12:45, 21 February 2008
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Human Methionine Aminopeptidase in complex with bengamide inhibitor LAF153 and cobalt
Overview
LAF389 is a synthetic analogue of bengamides, a class of marine natural products that produce inhibitory effects on tumor growth in vitro and in vivo. A proteomics-based approach has been used to identify signaling pathways affected by bengamides. LAF389 treatment of cells resulted in altered mobility of a subset of proteins on two-dimensional gel electrophoresis. Detailed analysis of one of the proteins, 14-3-3gamma, showed that bengamide treatment resulted in retention of the amino-terminal methionine, suggesting that bengamides directly or indirectly inhibited methionine aminopeptidases (MetAps). Both known MetAps are inhibited by LAF389. Short interfering RNA suppression of MetAp2 also altered amino-terminal processing of 14-3-3gamma. A high resolution structure of human MetAp2 co-crystallized with a bengamide shows that the compound binds in a manner that mimics peptide substrates. Additionally, the structure reveals that three key hydroxyl groups on the inhibitor coordinate the di-cobalt center in the enzyme active site.
About this Structure
1QZY 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
Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors., Towbin H, Bair KW, DeCaprio JA, Eck MJ, Kim S, Kinder FR, Morollo A, Mueller DR, Schindler P, Song HK, van Oostrum J, Versace RW, Voshol H, Wood J, Zabludoff S, Phillips PE, J Biol Chem. 2003 Dec 26;278(52):52964-71. Epub 2003 Oct 8. PMID:14534293
Page seeded by OCA on Thu Feb 21 14:45:36 2008
Categories: Homo sapiens | Methionyl aminopeptidase | Single protein | Eck, M J. | Morollo, A. | Song, H K. | CO | TBU | TDE | Hydrolase
