1r5h: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1r5h]] 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=1R5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R5H FirstGlance]. <br> | <table><tr><td colspan='2'>[[1r5h]] 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=1R5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R5H FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AO2:N-(2S,3R)-3-AMINO-4-CYCLOHEXYL-2-HYDROXY-BUTANO-N-(4-METHYLPHENYL)HYDRAZIDE'>AO2</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AO2:N-(2S,3R)-3-AMINO-4-CYCLOHEXYL-2-HYDROXY-BUTANO-N-(4-METHYLPHENYL)HYDRAZIDE'>AO2</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=1r5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r5h OCA], [https://pdbe.org/1r5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r5h RCSB], [https://www.ebi.ac.uk/pdbsum/1r5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r5h ProSAT]</span></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=1r5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r5h OCA], [https://pdbe.org/1r5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r5h RCSB], [https://www.ebi.ac.uk/pdbsum/1r5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r5h ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r5/1r5h_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r5/1r5h_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: BaMaung NY]] | |||
[[Category: BaMaung | [[Category: Craig RA]] | ||
[[Category: Craig | [[Category: Erickson SA]] | ||
[[Category: Erickson | [[Category: Henkin J]] | ||
[[Category: Henkin | [[Category: Kawai M]] | ||
[[Category: Kawai | [[Category: Kim KH]] | ||
[[Category: Kim | [[Category: Lesniewski R]] | ||
[[Category: Lesniewski | [[Category: Lou P]] | ||
[[Category: Lou | [[Category: Lynch L]] | ||
[[Category: Lynch | [[Category: Park C]] | ||
[[Category: Park | [[Category: Patel J]] | ||
[[Category: Patel | [[Category: Searle XB]] | ||
[[Category: Searle | [[Category: Sheppard GS]] | ||
[[Category: Sheppard | [[Category: Wang J]] | ||
[[Category: Wang | [[Category: Yang F]] | ||
[[Category: Yang | |||
Latest revision as of 10:17, 30 October 2024
Crystal Structure of MetAP2 complexed with A320282Crystal Structure of MetAP2 complexed with A320282
Structural highlights
FunctionMAP2_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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSubstituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing and cellular proliferation in human microvascular endothelial cells (HMVEC). 3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2.,Sheppard GS, Wang J, Kawai M, BaMaung NY, Craig RA, Erickson SA, Lynch L, Patel J, Yang F, Searle XB, Lou P, Park C, Kim KH, Henkin J, Lesniewski R Bioorg Med Chem Lett. 2004 Feb 23;14(4):865-8. PMID:15012983[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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