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1boa
From Proteopedia
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| - | [[Image:1boa.gif|left|200px]]<br /> | ||
| - | <applet load="1boa" size="450" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1boa, resolution 1.8Å" /> | ||
| - | '''HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH ANGIOGENESIS INHIBITOR FUMAGILLIN'''<br /> | ||
| - | == | + | ==HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH ANGIOGENESIS INHIBITOR FUMAGILLIN== |
| - | The fungal metabolite fumagillin suppresses the formation of new blood | + | <StructureSection load='1boa' size='340' side='right'caption='[[1boa]], [[Resolution|resolution]] 1.80Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1boa]] 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=1BOA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BOA FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | ||
| + | <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=FUG:FUMAGILLIN'>FUG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1boa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1boa OCA], [https://pdbe.org/1boa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1boa RCSB], [https://www.ebi.ac.uk/pdbsum/1boa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1boa ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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. | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bo/1boa_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=1boa ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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<ref>PMID:9812898</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1boa" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Clardy JC]] | ||
| + | [[Category: Crews CM]] | ||
| + | [[Category: Kemp CW]] | ||
| + | [[Category: Liu S]] | ||
| + | [[Category: Widom J]] | ||
Current revision
HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH ANGIOGENESIS INHIBITOR FUMAGILLIN
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Categories: Homo sapiens | Large Structures | Clardy JC | Crews CM | Kemp CW | Liu S | Widom J
