View source for 4pnc


==E. COLI METHIONINE AMINOPEPTIDASE IN COMPLEX WITH INHIBITOR 7-METHOXY-2-METHYLEN-3,4-DIHYDRONAPHTHALEN-1(2H)-ONE==
<StructureSection load='4pnc' size='340' side='right'caption='[[4pnc]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pnc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PNC 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]] 1.54&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7NP:(2S)-7-METHOXY-2-METHYL-3,4-DIHYDRONAPHTHALEN-1(2H)-ONE'>7NP</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4pnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pnc OCA], [https://pdbe.org/4pnc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pnc RCSB], [https://www.ebi.ac.uk/pdbsum/4pnc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pnc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C3TPN7_ECOLX C3TPN7_ECOLX] 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). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed (By similarity).[HAMAP-Rule:MF_01974]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We identified and characterized beta-aminoketones as prodrugs for irreversible MetAP inhibitors that are selective for the MetAP-1 subtype. beta-Aminoketones with certain structural features form alpha,beta-unsaturated ketones under physiological conditions, which bind covalently and selectively to cysteines in the S1 pocket of MetAP-1. The binding mode was confirmed by X-ray crystallography and assays with the MetAPs from Escherichia coli, Staphylococcus aureus and both human isoforms. The initially identified tetralone derivatives showed complete selectivity for E. coli MetAP versus human MetAP-1 and MetAP-2. Rational design of indanone analogs yielded compounds with selectivity for the human type-1 versus the human type-2 MetAP.

Beta-aminoketones as prodrugs for selective irreversible inhibitors of type-1 methionine aminopeptidases.,Altmeyer M, Amtmann E, Heyl C, Marschner A, Scheidig AJ, Klein CD Bioorg Med Chem Lett. 2014 Sep 23. pii: S0960-894X(14)00990-1. doi:, 10.1016/j.bmcl.2014.09.047. PMID:25293447<ref>PMID:25293447</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4pnc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Altmeyer M]]
[[Category: Klein CD]]
[[Category: Scheidig AJ]]