3pka: Difference between revisions

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<StructureSection load='3pka' size='340' side='right'caption='[[3pka]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
<StructureSection load='3pka' size='340' side='right'caption='[[3pka]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
== Structural highlights ==
== 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>
<table><tr><td colspan='2'>[[3pka]] 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=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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.25&#8491;</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='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='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>
<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>
</table>
== Function ==
== 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> 
[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>  
<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==
==See Also==
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Methionyl aminopeptidase]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Lu, J P]]
[[Category: Lu JP]]
[[Category: Ye, Q Z]]
[[Category: Ye QZ]]
[[Category: Hydrolase-hydrolase inhibitor complex]]

Latest revision as of 13:41, 21 February 2024

M. tuberculosis MetAP with bengamide analog Y02, in Mn formM. tuberculosis MetAP with bengamide analog Y02, in Mn form

Structural highlights

3pka is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.25Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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][1] [2]

See Also

References

  1. ↑ Zhang X, Chen S, Hu Z, Zhang L, Wang H. Expression and characterization of two functional methionine aminopeptidases from Mycobacterium tuberculosis H37Rv. Curr Microbiol. 2009 Nov;59(5):520-5. doi: 10.1007/s00284-009-9470-3. Epub 2009, Aug 18. PMID:19688379 doi:10.1007/s00284-009-9470-3
  2. ↑ Lu JP, Chai SC, Ye QZ. Catalysis and Inhibition of Mycobacterium tuberculosis Methionine Aminopeptidase. J Med Chem. 2009 Dec 28. PMID:20038112 doi:10.1021/jm901624n

3pka, resolution 1.25Å

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