1qzy

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{{STRUCTURE_1qzy| PDB=1qzy | SCENE= }}
{{STRUCTURE_1qzy| PDB=1qzy | SCENE= }}
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'''Human Methionine Aminopeptidase in complex with bengamide inhibitor LAF153 and cobalt'''
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===Human Methionine Aminopeptidase in complex with bengamide inhibitor LAF153 and cobalt===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 14534293 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14534293}}
==About this Structure==
==About this Structure==
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[[Category: Song, H K.]]
[[Category: Song, H K.]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:54:27 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:50:30 2008''

Revision as of 09:50, 29 July 2008

Image:1qzy.png

Template:STRUCTURE 1qzy

Human Methionine Aminopeptidase in complex with bengamide inhibitor LAF153 and cobalt

Template:ABSTRACT PUBMED 14534293

About this Structure

1QZY is a Single protein structure of sequence from Homo sapiens. 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

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