View source for 4iec


==Cys105 covalent modification by 2-hydroxyethyl disulfide in Mycobacterium tuberculosis methionine aminopeptidase Type 1c==
<StructureSection load='4iec' size='340' side='right'caption='[[4iec]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4iec]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IEC 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=4iec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iec OCA], [https://pdbe.org/4iec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iec RCSB], [https://www.ebi.ac.uk/pdbsum/4iec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iec ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MAP12_MYCTU MAP12_MYCTU] 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.[HAMAP-Rule:MF_01974]<ref>PMID:19688379</ref> <ref>PMID:20038112</ref> 
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== Publication Abstract from PubMed ==
Methionine aminopeptidases (MetAPs) cleave initiator methionine from ~ 70% of the newly synthesized proteins in every living cell, and specific inhibition or knockdown of this function is detrimental. MetAPs are metalloenzymes, and are broadly classified into two subtypes, type I and type II. Bacteria contain only type I MetAPs, and the active site of these enzymes contains a conserved cysteine. By contrast, in type II enzymes the analogous position is occupied by a conserved glycine. Here, we report the reactivity of the active site cysteine in a type I MetAP, MetAP1c, of Mycobacterium tuberculosis (MtMetAP1c) towards highly selective cysteine-specific reagents. The authenticity of selective modification of Cys105 of MtMetAP1c was established by using site-directed mutagenesis and crystal structure determination of covalent and noncovalent complexes. On the basis of these observations, we propose that metal ions in the active site assist in the covalent modification of Cys105 by orienting the reagents appropriately for a successful reaction. These studies establish, for the first time, that the conserved cysteine of type I MetAPs can be targeted for selective inhibition, and we believe that this chemistry can be exploited for further drug discovery efforts regarding microbial MetAPs.

Selective targeting of the conserved active site cysteine of Mycobacterium tuberculosis methionine aminopeptidase with electrophilic reagents.,Reddi R, Arya T, Kishor C, Gumpena R, Ganji RJ, Bhukya S, Addlagatta A FEBS J. 2014 Sep;281(18):4240-8. doi: 10.1111/febs.12847. Epub 2014 Jun 6. PMID:24841365<ref>PMID:24841365</ref>

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

==See Also==
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Addlagatta A]]
[[Category: Gumpena R]]
[[Category: Kishor C]]
[[Category: Reddi R]]