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1qzy

From Proteopedia

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[[Image:1qzy.jpg|left|200px]]<br /><applet load="1qzy" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1qzy, resolution 1.60&Aring;" />
 
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'''Human Methionine Aminopeptidase in complex with bengamide inhibitor LAF153 and cobalt'''<br />
 
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==Overview==
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==Human Methionine Aminopeptidase in complex with bengamide inhibitor LAF153 and cobalt==
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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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<StructureSection load='1qzy' size='340' side='right'caption='[[1qzy]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1qzy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QZY FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=TBU:TERTIARY-BUTYL+ALCOHOL'>TBU</scene>, <scene name='pdbligand=TDE:(E)-(2R,3R,4S,5R)-3,4,5-TRIHYDROXY-2-METHOXY-8,8-DIMETHYL-NON-6-ENOIC+ACID+((3S,6R)-6-HYDROXY-2-OXO-AZEPAN-3-YL)-AMIDE'>TDE</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qzy OCA], [https://pdbe.org/1qzy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qzy RCSB], [https://www.ebi.ac.uk/pdbsum/1qzy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qzy ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MAP2_HUMAN MAP2_HUMAN] Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo. Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qz/1qzy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1qzy ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1QZY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CO:'>CO</scene>, <scene name='pdbligand=TDE:'>TDE</scene> and <scene name='pdbligand=TBU:'>TBU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QZY OCA].
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*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14534293 14534293]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Methionyl aminopeptidase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Eck MJ]]
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[[Category: Eck, M.J.]]
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[[Category: Morollo A]]
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[[Category: Morollo, A.]]
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[[Category: Song HK]]
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[[Category: Song, H.K.]]
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[[Category: CO]]
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[[Category: TBU]]
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[[Category: TDE]]
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[[Category: hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:46:39 2008''
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Current revision

Human Methionine Aminopeptidase in complex with bengamide inhibitor LAF153 and cobalt

PDB ID 1qzy

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