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==Human Methionine Aminopeptidase Complex with 4-Aryl-1,2,3-triazole Inhibitor== | |||
<StructureSection load='2adu' size='340' side='right'caption='[[2adu]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2adu]] 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=2ADU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ADU 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]] 1.9Å</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=R20:4-(3-METHYLPHENYL)-1H-1,2,3-TRIAZOLE'>R20</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=2adu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2adu OCA], [https://pdbe.org/2adu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2adu RCSB], [https://www.ebi.ac.uk/pdbsum/2adu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2adu 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/ad/2adu_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2adu ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo. | |||
4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.,Kallander LS, Lu Q, Chen W, Tomaszek T, Yang G, Tew D, Meek TD, Hofmann GA, Schulz-Pritchard CK, Smith WW, Janson CA, Ryan MD, Zhang GF, Johanson KO, Kirkpatrick RB, Ho TF, Fisher PW, Mattern MR, Johnson RK, Hansbury MJ, Winkler JD, Ward KW, Veber DF, Thompson SK J Med Chem. 2005 Sep 8;48(18):5644-7. PMID:16134930<ref>PMID:16134930</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2adu" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Chen W]] | |||
[[Category: Chen | [[Category: Fisher PW]] | ||
[[Category: Fisher | [[Category: Hansbury MJ]] | ||
[[Category: Hansbury | [[Category: Ho TF]] | ||
[[Category: Ho | [[Category: Hofmann GA]] | ||
[[Category: Hofmann | [[Category: Janson CA]] | ||
[[Category: Janson | [[Category: Johanson KO]] | ||
[[Category: Johanson | [[Category: Johnson RK]] | ||
[[Category: Johnson | [[Category: Kallander LS]] | ||
[[Category: Kallander | [[Category: Kirkpatrick RB]] | ||
[[Category: Kirkpatrick | [[Category: Lu Q]] | ||
[[Category: Lu | [[Category: Mattern MR]] | ||
[[Category: Mattern | [[Category: Meek TD]] | ||
[[Category: Meek | [[Category: Ryan MD]] | ||
[[Category: Ryan | [[Category: Schulz-Pritchard CK]] | ||
[[Category: Schulz-Pritchard | [[Category: Smith WW]] | ||
[[Category: Smith | [[Category: Tew D]] | ||
[[Category: Tew | [[Category: Thompson SK]] | ||
[[Category: Thompson | [[Category: Tomaszek T]] | ||
[[Category: Tomaszek | [[Category: Veber DF]] | ||
[[Category: Veber | [[Category: Ward KW]] | ||
[[Category: Ward | [[Category: Winkler JD]] | ||
[[Category: Winkler | [[Category: Yang G]] | ||
[[Category: Yang | [[Category: Zhang GF]] | ||
[[Category: Zhang | |||
Latest revision as of 10:48, 30 October 2024
Human Methionine Aminopeptidase Complex with 4-Aryl-1,2,3-triazole InhibitorHuman Methionine Aminopeptidase Complex with 4-Aryl-1,2,3-triazole Inhibitor
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 PubMedInhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo. 4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.,Kallander LS, Lu Q, Chen W, Tomaszek T, Yang G, Tew D, Meek TD, Hofmann GA, Schulz-Pritchard CK, Smith WW, Janson CA, Ryan MD, Zhang GF, Johanson KO, Kirkpatrick RB, Ho TF, Fisher PW, Mattern MR, Johnson RK, Hansbury MJ, Winkler JD, Ward KW, Veber DF, Thompson SK J Med Chem. 2005 Sep 8;48(18):5644-7. PMID:16134930[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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