5ji6: Difference between revisions
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<StructureSection load='5ji6' size='340' side='right' caption='[[5ji6]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='5ji6' size='340' side='right' caption='[[5ji6]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ji6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JI6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JI6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5ji6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JI6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JI6 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6KN:4-(3-METHYLPYRIDIN-4-YL)-6-(TRIFLUOROMETHYL)-1H-INDAZOLE'>6KN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6KN:4-(3-METHYLPYRIDIN-4-YL)-6-(TRIFLUOROMETHYL)-1H-INDAZOLE'>6KN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jhu|5jhu]], [[5jfr|5jfr]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jhu|5jhu]], [[5jfr|5jfr]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METAP2, MNPEP, P67EIF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ji6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ji6 OCA], [http://pdbe.org/5ji6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ji6 RCSB], [http://www.ebi.ac.uk/pdbsum/5ji6 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ji6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ji6 OCA], [http://pdbe.org/5ji6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ji6 RCSB], [http://www.ebi.ac.uk/pdbsum/5ji6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ji6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Methionyl aminopeptidase]] | [[Category: Methionyl aminopeptidase]] | ||
[[Category: Dougan, D R]] | [[Category: Dougan, D R]] | ||
Revision as of 13:03, 22 November 2017
Potent, Reversible MetAP2 Inhibitors via FBDDPotent, Reversible MetAP2 Inhibitors via FBDD
Structural highlights
Function[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. Publication Abstract from PubMedMethionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and structural biology to quickly identify and elaborate an indazole fragment into a series of reversible MetAP2 inhibitors with <10nM potency, excellent selectivity, and favorable in vitro safety profiles. Discovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design-Part 1.,Cheruvallath Z, Tang M, McBride C, Komandla M, Miura J, Ton-Nu T, Erikson P, Feng J, Farrell P, Lawson JD, Vanderpool D, Wu Y, Dougan DR, Plonowski A, Holub C, Larson C Bioorg Med Chem Lett. 2016 Jun 15;26(12):2774-8. doi: 10.1016/j.bmcl.2016.04.073., Epub 2016 Apr 25. PMID:27155900[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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