This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1b6a
From Proteopedia
(Difference between revisions)
(New page: 200px<br /> <applet load="1b6a" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b6a, resolution 1.60Å" /> '''HUMAN METHIONINE AM...) |
|||
| (18 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | [[Image:1b6a.gif|left|200px]]<br /> | ||
| - | <applet load="1b6a" size="450" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1b6a, resolution 1.60Å" /> | ||
| - | '''HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470'''<br /> | ||
| - | == | + | ==HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470== |
| - | The fungal metabolite fumagillin suppresses the formation of new blood | + | <StructureSection load='1b6a' size='340' side='right'caption='[[1b6a]], [[Resolution|resolution]] 1.60Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1b6a]] 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=1B6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B6A 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]] 1.6Å</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=TN4:(1R,2S,3S,4R)-4-HYDROXY-2-METHOXY-4-METHYL-3-[(2R,3R)-2-METHYL-3-(3-METHYLBUT-2-EN-1-YL)OXIRAN-2-YL]CYCLOHEXYL+(CHLOROACETYL)CARBAMATE'>TN4</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=1b6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b6a OCA], [https://pdbe.org/1b6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b6a RCSB], [https://www.ebi.ac.uk/pdbsum/1b6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b6a 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/b6/1b6a_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=1b6a 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> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1b6a" style="background-color:#fffaf0;"></div> | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ==See Also== | |
| + | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Clardy JC]] | ||
| + | [[Category: Liu S]] | ||
Current revision
HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470
| |||||||||||
