5yr6: Difference between revisions

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-'''Unreleased structure'''
-The entry 5yr6 is ON HOLD
+==Human methionine aminopeptidase type 1b (F309L mutant) in complex with TNP470==
+<StructureSection load='5yr6' size='340' side='right'caption='[[5yr6]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5yr6]] 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=5YR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YR6 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]] 1.75&#8491;</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=NA:SODIUM+ION'>NA</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=5yr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yr6 OCA], [https://pdbe.org/5yr6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yr6 RCSB], [https://www.ebi.ac.uk/pdbsum/5yr6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yr6 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Natural product ovalicin and its synthetic derivative TNP-470 have been extensively studied for their anti-angiogenic property, and the later reached phase 3 clinical trials. They covalently modify the conserved histidine in Type 2 methionine aminopeptidases (MetAPs) at nanomolar concentrations. Even though a similar mechanism is possible in Type 1 human MetAP, it is inhibited only at millimolar concentration. In this study, we have discovered two Type 1 wild type MetAPs ( S. pneumoniae and E. faecalis ) that are inhibited at low micromolar to nanomolar concentrations, and established the molecular mechanism. F309 in the active site of human Type 1 MetAP ( Hs MetAP1b) seems to be the key to the resistance, while newly identified ovalicin sensitive Type 1 MetAPs have a methionine or isoleucine at this position. Type 2 human MetAP ( Hs MetAP2) also has an isoleucine (I338) in the analogous position. Ovalicin inhibited F309M and F309I mutants of human MetAP1b at low micromolar concentration. MD simulations suggest that ovalicin is not stably placed in the active site of wild type MetAP1b before the covalent modification. In the case of F309M mutant and human Type 2 MetAP, molecule spends more time in the active site providing time for covalent modification.
-Authors:
+Discovery of Natural Product Ovalicin Sensitive Type 1 Methionine Aminopeptidases: Molecular and Structural Basis.,Pillalamarri V, Arya T, Haque N, Bala SC, Marapaka AK, Addlagatta A Biochem J. 2019 Mar 5. pii: BCJ20180874. doi: 10.1042/BCJ20180874. PMID:30837307<ref>PMID:30837307</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5yr6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Addlagatta A]]
+[[Category: Arya T]]
+[[Category: Pillalamarri V]]