4iks

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<StructureSection load='4iks' size='340' side='right'caption='[[4iks]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
<StructureSection load='4iks' size='340' side='right'caption='[[4iks]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4iks]] 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=4IKS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IKS FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4iks]] 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=4IKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IKS FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TFD:N-[5-CHLORO-6-METHYL-2-(PYRIDIN-2-YL)PYRIMIDIN-4-YL]-N-[6-(TRIFLUOROMETHYL)PYRIDIN-2-YL]ETHANE-1,2-DIAMINE'>TFD</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ikr|4ikr]], [[4ikt|4ikt]], [[4iku|4iku]]</td></tr>
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<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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TFD:N-[5-CHLORO-6-METHYL-2-(PYRIDIN-2-YL)PYRIMIDIN-4-YL]-N-[6-(TRIFLUOROMETHYL)PYRIDIN-2-YL]ETHANE-1,2-DIAMINE'>TFD</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METAP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4iks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iks OCA], [https://pdbe.org/4iks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iks RCSB], [https://www.ebi.ac.uk/pdbsum/4iks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iks ProSAT]</span></td></tr>
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<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>
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<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=4iks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iks OCA], [http://pdbe.org/4iks PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iks RCSB], [http://www.ebi.ac.uk/pdbsum/4iks PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iks ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/AMPM1_HUMAN AMPM1_HUMAN]] Removes the N-terminal methionine from nascent proteins. Required for normal progression through the cell cycle.<ref>PMID:16274222</ref> <ref>PMID:17114291</ref>
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[https://www.uniprot.org/uniprot/MAP11_HUMAN MAP11_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). Required for normal progression through the cell cycle.[HAMAP-Rule:MF_03174]<ref>PMID:16274222</ref> <ref>PMID:17114291</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Methionine aminopeptidases (MetAPs) are essential enzymes that make them good drug targets in cancer and microbial infections. MetAPs remove the initiator methionine from newly synthesized peptides in every living cell. MetAPs are broadly divided into type I and type II classes. Both prokaryotes and eukaryotes contain type I MetAPs, while eukaryotes have additional type II MetAP enzyme. Although several inhibitors have been reported against type I enzymes, subclass specificity is scarce. Here, using the fine differences in the entrance of the active sites of MetAPs from Mycobacterium tuberculosis , Enterococcus faecalis , and human, three hotspots have been identified and pyridinylpyrimidine-based molecules were selected from a commercial source to target these hotspots. In the biochemical evaluation, many of the 38 compounds displayed differential behavior against these three enzymes. Crystal structures of four selected inhibitors in complex with human MetAP1b and molecular modeling studies provided the basis for the binding specificity.
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Identification, Biochemical and Structural Evaluation of Species-Specific Inhibitors against Type I Methionine Aminopeptidases.,Kishor C, Arya T, Reddi R, Chen X, Saddanapu V, Marapaka AK, Gumpena R, Ma D, Liu JO, Addlagatta A J Med Chem. 2013 Jun 27. PMID:23767698<ref>PMID:23767698</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4iks" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Methionyl aminopeptidase]]
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[[Category: Addlagatta A]]
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[[Category: Addlagatta, A]]
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[[Category: Arya T]]
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[[Category: Arya, T]]
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[[Category: Kishor C]]
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[[Category: Kishor, C]]
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[[Category: Aminopeptidase]]
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[[Category: Hydrolase]]
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[[Category: Pita-bread fold]]
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[[Category: Ribosome]]
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Current revision

Crystal structure of truncated (delta 1-89) human methionine aminopeptidase Type 1 in complex with N1-(5-chloro-6-methyl-2-(pyridin-2-yl)pyrimidin-4-yl)-N2-(6-(trifluoromethyl)pyridin-2-yl)ethane-1,2-diamine

PDB ID 4iks

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