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| | <StructureSection load='1epv' size='340' side='right'caption='[[1epv]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='1epv' size='340' side='right'caption='[[1epv]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1epv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EPV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EPV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1epv]] 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=1EPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EPV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DCS:D-[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHYL]-N,O-CYCLOSERYLAMIDE'>DCS</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]] 2.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | + | <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> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sft|1sft]]</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=1epv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1epv OCA], [https://pdbe.org/1epv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1epv RCSB], [https://www.ebi.ac.uk/pdbsum/1epv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1epv ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1epv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1epv OCA], [http://pdbe.org/1epv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1epv RCSB], [http://www.ebi.ac.uk/pdbsum/1epv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1epv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ep/1epv_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ep/1epv_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alanine racemase]] | + | [[Category: Geobacillus stearothermophilus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fenn, T D]] | + | [[Category: Fenn TD]] |
| - | [[Category: Morollo, A A]] | + | [[Category: Morollo AA]] |
| - | [[Category: Ringe, D]] | + | [[Category: Ringe D]] |
| - | [[Category: Stamper, G F]] | + | [[Category: Stamper GF]] |
| - | [[Category: Alpha-beta barrel]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| Structural highlights
Function
ALR_GEOSE Catalyzes the interconversion of L-alanine and D-alanine. Also weakly active on serine.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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:12741835[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Watanabe A, Yoshimura T, Mikami B, Esaki N. Tyrosine 265 of alanine racemase serves as a base abstracting alpha-hydrogen from L-alanine: the counterpart residue to lysine 39 specific to D-alanine. J Biochem. 1999 Oct;126(4):781-6. PMID:10502689
- ↑ Patrick WM, Weisner J, Blackburn JM. Site-directed mutagenesis of Tyr354 in Geobacillus stearothermophilus alanine racemase identifies a role in controlling substrate specificity and a possible role in the evolution of antibiotic resistance. Chembiochem. 2002 Aug 2;3(8):789-92. PMID:12203980 doi:<789::AID-CBIC789>3.0.CO;2-D http://dx.doi.org/10.1002/1439-7633(20020802)3:8<789::AID-CBIC789>3.0.CO;2-D
- ↑ Fenn TD, Stamper GF, Morollo AA, Ringe D. A side reaction of alanine racemase: transamination of cycloserine. Biochemistry. 2003 May 20;42(19):5775-83. PMID:12741835 doi:10.1021/bi027022d
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