View source for 3pka


==M. tuberculosis MetAP with bengamide analog Y02, in Mn form==
<StructureSection load='3pka' size='340' side='right'caption='[[3pka]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pka]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PKA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Y02:(2R,3R,4S,5R,6E)-3,4,5-TRIHYDROXY-2-METHOXY-8,8-DIMETHYL-N-[2-(2,4,6-TRIMETHYLPHENOXY)ETHYL]NON-6-ENAMIDE'>Y02</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3iu7|3iu7]], [[3iu8|3iu8]], [[3iu9|3iu9]], [[3pke|3pke]], [[3pkb|3pkb]], [[3pkc|3pkc]], [[3pkd|3pkd]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">map, mapB, MT2929, MTV003.07c, Rv2861c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3pka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pka OCA], [https://pdbe.org/3pka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pka RCSB], [https://www.ebi.ac.uk/pdbsum/3pka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pka ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/AMPM2_MYCTU AMPM2_MYCTU]] Removes the N-terminal methionine from nascent proteins, when the penultimate amino acid is alanine or proline, but enzyme activity is remarkably low when the second residue is phenylalanine or leucine. With glycine at the second position, Map is more active with a tetrapeptide than with a tripeptide.<ref>PMID:19688379</ref> <ref>PMID:20038112</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Methionine aminopeptidase (MetAP) carries out an essential function of protein N-terminal processing in many bacteria and is a promising target for the development of novel antitubercular agents. Natural bengamides potently inhibit the proliferation of mammalian cells by targeting MetAP enzymes, and the X-ray crystal structure of human type 2 MetAP in complex with a bengamide derivative reveals the key interactions at the active site. By preserving the interactions with the conserved residues inside the binding pocket while exploring the differences between bacterial and human MetAPs around the binding pocket, seven bengamide derivatives were synthesized and evaluated for inhibition of MtMetAP1a and MtMetAP1c in different metalloforms, inhibition of M. tuberculosis growth in replicating and non-replicating states, and inhibition of human K562 cell growth. Potent inhibition of MtMetAP1a and MtMetAP1c and modest growth inhibition of M. tuberculosis were observed for some of these derivatives. Crystal structures of MtMetAP1c in complex with two of the derivatives provided valuable structural information for improvement of these inhibitors for potency and selectivity.

Inhibition of Mycobacterium tuberculosis Methionine Aminopeptidases by Bengamide Derivatives.,Lu JP, Yuan XH, Yuan H, Wang WL, Wan B, Franzblau SG, Ye QZ ChemMedChem. 2011 Apr 4. doi: 10.1002/cmdc.201100003. PMID:21465667<ref>PMID:21465667</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pka" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Methionyl aminopeptidase]]
[[Category: Lu, J P]]
[[Category: Ye, Q Z]]
[[Category: Hydrolase-hydrolase inhibitor complex]]