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1niu

From Proteopedia

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(New page: 200px<br /><applet load="1niu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1niu, resolution 2.20&Aring;" /> '''ALANINE RACEMASE WIT...)
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[[Image:1niu.gif|left|200px]]<br /><applet load="1niu" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1niu, resolution 2.20&Aring;" />
 
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'''ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM L-CYCLOSERINE'''<br />
 
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==Overview==
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==ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM L-CYCLOSERINE==
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Alanine racemase (EC 5.1.1.1) catalyzes the interconversion of alanine, enantiomers, and thus represents the first committed step involved in, bacterial cell wall biosynthesis. Cycloserine acts as a suicide inhibitor, of alanine racemase and as such, serves as an antimicrobial agent. The, chemical means by which cycloserine inhibits alanine racemase is unknown., Through spectroscopic assays, we show here evidence of a pyridoxal, derivative (arising from either isomer of cycloserine) saturated at the, C4' carbon position. We additionally report the L- and D-cycloserine, inactivated crystal structures of Bacillus stearothermophilus alanine, racemase, which corroborates the spectroscopy via evidence of a, 3-hydroxyisoxazole pyridoxamine derivative. Upon the basis of the kinetic, and structural properties of both the L- and D-isomers of the inhibitor, we propose a mechanism of alanine racemase inactivation by cycloserine., This pathway involves an initial transamination step followed by, tautomerization to form a stable aromatic adduct, a scheme similar to that, seen in cycloserine inactivation of aminotransferases.
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<StructureSection load='1niu' size='340' side='right'caption='[[1niu]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1niu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NIU FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCS:D-[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHYL]-N,O-CYCLOSERYLAMIDE'>DCS</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1niu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1niu OCA], [https://pdbe.org/1niu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1niu RCSB], [https://www.ebi.ac.uk/pdbsum/1niu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1niu ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ALR_GEOSE ALR_GEOSE] Catalyzes the interconversion of L-alanine and D-alanine. Also weakly active on serine.<ref>PMID:10502689</ref> <ref>PMID:12203980</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ni/1niu_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1niu ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1NIU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with DCS as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Alanine_racemase Alanine racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.1 5.1.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NIU OCA].
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*[[Alanine racemase 3D structures|Alanine racemase 3D structures]]
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== References ==
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==Reference==
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<references/>
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A side reaction of alanine racemase: transamination of cycloserine., Fenn TD, Stamper GF, Morollo AA, Ringe D, Biochemistry. 2003 May 20;42(19):5775-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12741835 12741835]
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__TOC__
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[[Category: Alanine racemase]]
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</StructureSection>
[[Category: Geobacillus stearothermophilus]]
[[Category: Geobacillus stearothermophilus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Fenn, T.D.]]
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[[Category: Fenn TD]]
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[[Category: Morollo, A.A.]]
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[[Category: Morollo AA]]
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[[Category: Ringe, D.]]
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[[Category: Ringe D]]
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[[Category: Stamper, G.F.]]
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[[Category: Stamper GF]]
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[[Category: DCS]]
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[[Category: plp-containing]]
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[[Category: tim barrel]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 22:18:11 2007''
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Current revision

ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM L-CYCLOSERINE

PDB ID 1niu

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