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[[Image:2ggc.gif|left|200px]]
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{{STRUCTURE_2ggc|  PDB=2ggc  |  SCENE=  }}
'''Novel bacterial methionine aminopeptidase inhibitors'''


==Novel bacterial methionine aminopeptidase inhibitors==
<StructureSection load='2ggc' size='340' side='right'caption='[[2ggc]], [[Resolution|resolution]] 1.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ggc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GGC 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&#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=MET:METHIONINE'>MET</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=2ggc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ggc OCA], [https://pdbe.org/2ggc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ggc RCSB], [https://www.ebi.ac.uk/pdbsum/2ggc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ggc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MAP1_ECOLI MAP1_ECOLI] 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:20521764</ref> <ref>PMID:3027045</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gg/2ggc_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ggc ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In this article we describe the application of structural biology methods to the discovery of novel potent inhibitors of methionine aminopeptidases. These enzymes are employed by the cells to cleave the N-terminal methionine from nascent peptides and proteins. As this is one of the critical steps in protein maturation, it is very likely that inhibitors of these enzymes may prove useful as novel antibacterial agents. Involvement of crystallography at the very early stages of the inhibitor design process resulted in serendipitous discovery of a new inhibitor class, the pyrazole-diamines. Atomic-resolution structures of several inhibitors bound to the enzyme illuminate a new mode of inhibitor binding.


==Overview==
Serendipitous discovery of novel bacterial methionine aminopeptidase inhibitors.,Evdokimov AG, Pokross M, Walter RL, Mekel M, Barnett BL, Amburgey J, Seibel WL, Soper SJ, Djung JF, Fairweather N, Diven C, Rastogi V, Grinius L, Klanke C, Siehnel R, Twinem T, Andrews R, Curnow A Proteins. 2007 Feb 15;66(3):538-46. PMID:17120228<ref>PMID:17120228</ref>
In this article we describe the application of structural biology methods to the discovery of novel potent inhibitors of methionine aminopeptidases. These enzymes are employed by the cells to cleave the N-terminal methionine from nascent peptides and proteins. As this is one of the critical steps in protein maturation, it is very likely that inhibitors of these enzymes may prove useful as novel antibacterial agents. Involvement of crystallography at the very early stages of the inhibitor design process resulted in serendipitous discovery of a new inhibitor class, the pyrazole-diamines. Atomic-resolution structures of several inhibitors bound to the enzyme illuminate a new mode of inhibitor binding.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2GGC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GGC OCA].
</div>
<div class="pdbe-citations 2ggc" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Serendipitous discovery of novel bacterial methionine aminopeptidase inhibitors., Evdokimov AG, Pokross M, Walter RL, Mekel M, Barnett BL, Amburgey J, Seibel WL, Soper SJ, Djung JF, Fairweather N, Diven C, Rastogi V, Grinius L, Klanke C, Siehnel R, Twinem T, Andrews R, Curnow A, Proteins. 2007 Feb 15;66(3):538-46. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17120228 17120228]
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
[[Category: Escherichia coli]]
== References ==
[[Category: Methionyl aminopeptidase]]
<references/>
[[Category: Single protein]]
__TOC__
[[Category: Evdokimov, A G.]]
</StructureSection>
[[Category: Mekel, M.]]
[[Category: Escherichia coli K-12]]
[[Category: Pokross, M E.]]
[[Category: Large Structures]]
[[Category: Walter, R L.]]
[[Category: Evdokimov AG]]
[[Category: Antibacterial]]
[[Category: Mekel M]]
[[Category: Map inhibitor]]
[[Category: Pokross ME]]
[[Category: Methionine amino peptidase]]
[[Category: Walter RL]]
[[Category: Pita-bread fold]]
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