2bww: Difference between revisions

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-[[Image:2bww.gif|left|200px]]<br /><applet load="2bww" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2bww, resolution 2.61&Aring;" />
-'''HIS350ALA ESCHERICHIA COLI AMINOPEPTIDASE P'''<br />
-==Overview==
+==His350Ala Escherichia coli Aminopeptidase P==
-Aminopeptidase P (APPro) is a manganese-dependent enzyme that cleaves the, N-terminal amino acid from polypeptides where the second residue is, proline. APPro shares a similar fold, substrate specificity, and catalytic, mechanism with methionine aminopeptidase and prolidase. To investigate the, roles of conserved residues at the active site, seven mutant forms of, APPro were characterized kinetically and structurally. Mutation of, individual metal ligands selectively abolished binding of either or both, Mn(II) atoms at the active site, and none of these metal-ligand mutants, had detectable catalytic activity. Mutation of the conserved active site, residues His243 and His361 revealed that both are required for catalysis., We propose that His243 stabilizes substrate binding through an interaction, with the carbonyl oxygen of the requisite proline residue of a substrate, and that His361 stabilizes substrate binding and the gem-diol catalytic, intermediate. Sequence, structural, and kinetic analyses reveal that, His350, conserved in APPro and prolidase but not in methionine, aminopeptidase, forms part of a hydrophobic binding pocket that gives, APPro its proline specificity. Further, peptides in which the required, proline residue is replaced by N-methylalanine or alanine are cleaved by, APPro, but they are extremely poor substrates due to a loss of, interactions between the prolidyl ring of the substrate and the, hydrophobic proline-binding pocket.
+<StructureSection load='2bww' size='340' side='right'caption='[[2bww]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2bww]] 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=2BWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BWW 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]] 2.61&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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=2bww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bww OCA], [https://pdbe.org/2bww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bww RCSB], [https://www.ebi.ac.uk/pdbsum/2bww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bww ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/AMPP_ECOLI AMPP_ECOLI]
+== 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/bw/2bww_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=2bww ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Aminopeptidase P (APPro) is a manganese-dependent enzyme that cleaves the N-terminal amino acid from polypeptides where the second residue is proline. APPro shares a similar fold, substrate specificity, and catalytic mechanism with methionine aminopeptidase and prolidase. To investigate the roles of conserved residues at the active site, seven mutant forms of APPro were characterized kinetically and structurally. Mutation of individual metal ligands selectively abolished binding of either or both Mn(II) atoms at the active site, and none of these metal-ligand mutants had detectable catalytic activity. Mutation of the conserved active site residues His243 and His361 revealed that both are required for catalysis. We propose that His243 stabilizes substrate binding through an interaction with the carbonyl oxygen of the requisite proline residue of a substrate and that His361 stabilizes substrate binding and the gem-diol catalytic intermediate. Sequence, structural, and kinetic analyses reveal that His350, conserved in APPro and prolidase but not in methionine aminopeptidase, forms part of a hydrophobic binding pocket that gives APPro its proline specificity. Further, peptides in which the required proline residue is replaced by N-methylalanine or alanine are cleaved by APPro, but they are extremely poor substrates due to a loss of interactions between the prolidyl ring of the substrate and the hydrophobic proline-binding pocket.
-==About this Structure==
+Kinetic and crystallographic analysis of mutant Escherichia coli aminopeptidase P: insights into substrate recognition and the mechanism of catalysis.,Graham SC, Lilley PE, Lee M, Schaeffer PM, Kralicek AV, Dixon NE, Guss JM Biochemistry. 2006 Jan 24;45(3):964-75. PMID:16411772<ref>PMID:16411772</ref>
-BWW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=FLC:'>FLC</scene> and <scene name='pdbligand=MRD:'>MRD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Xaa-Pro_aminopeptidase Xaa-Pro aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.9 3.4.11.9] Known structural/functional Site: <scene name='pdbsite=AC1:Mrd+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BWW OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Kinetic and crystallographic analysis of mutant Escherichia coli aminopeptidase P: insights into substrate recognition and the mechanism of catalysis., Graham SC, Lilley PE, Lee M, Schaeffer PM, Kralicek AV, Dixon NE, Guss JM, Biochemistry. 2006 Jan 24;45(3):964-75. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16411772 16411772]
+</div>
+<div class="pdbe-citations 2bww" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Escherichia coli]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Xaa-Pro aminopeptidase]]
+[[Category: Graham SC]]
-[[Category: Graham, S.C.]]
+[[Category: Guss JM]]
-[[Category: Guss, J.M.]]
-[[Category: FLC]]
-[[Category: MG]]
-[[Category: MN]]
-[[Category: MRD]]
-[[Category: 'pita-bread' enzyme]]
-[[Category: aminopeptidase p]]
-[[Category: hydrolase]]
-[[Category: manganese enzyme]]
-[[Category: metalloenzyme]]
-[[Category: proline-specific enzyme]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:28:45 2008''