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| | <StructureSection load='1xqk' size='340' side='right'caption='[[1xqk]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='1xqk' size='340' side='right'caption='[[1xqk]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xqk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_12980 Atcc 12980]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XQK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xqk]] 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=1XQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XQK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PMH:(5-HYDROXY-4-{[(3-HYDROXYISOXAZOL-4-YL)AMINO]METHYL}-6-METHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>PMH</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]] 1.95Å</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=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=PMH:(5-HYDROXY-4-{[(3-HYDROXYISOXAZOL-4-YL)AMINO]METHYL}-6-METHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>PMH</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1sft|1sft]], [[1xql|1xql]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alr, dal ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1422 ATCC 12980])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Alanine_racemase Alanine racemase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1xqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xqk OCA], [https://pdbe.org/1xqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xqk RCSB], [https://www.ebi.ac.uk/pdbsum/1xqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xqk 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=1xqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xqk OCA], [https://pdbe.org/1xqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xqk RCSB], [https://www.ebi.ac.uk/pdbsum/1xqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xqk ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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]] |
| Line 39: |
Line 36: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alanine racemase]] | + | [[Category: Geobacillus stearothermophilus]] |
| - | [[Category: Atcc 12980]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fenn, T D]] | + | [[Category: Fenn TD]] |
| - | [[Category: Holyoak, T]] | + | [[Category: Holyoak T]] |
| - | [[Category: Ringe, D]] | + | [[Category: Ringe D]] |
| - | [[Category: Stamper, G F]] | + | [[Category: Stamper GF]] |
| - | [[Category: Cycloserine]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| 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
The requirement for d-alanine in the peptidoglycan layer of bacterial cell walls is fulfilled in part by alanine racemase (EC 5.1.1.1), a pyridoxal 5'-phosphate (PLP)-assisted enzyme. The enzyme utilizes two antiparallel bases focused at the C(alpha) position and oriented perpendicular to the PLP ring to facilitate the equilibration of alanine enantiomers. Understanding how this two-base system is utilized and controlled to yield reaction specificity is therefore a potential means for designing antibiotics. Cycloserine is a known alanine racemase suicide substrate, although its mechanism of inactivation is based on transaminase chemistry. Here we characterize the effects of a Y265F mutant (Tyr265 acts as the catalytic base in the l-isomer case) of Bacillus stearothermophilus alanine racemase on cycloserine inactivation. The Y265F mutant reduces racemization activity 1600-fold [Watanabe, A., Yoshimura, T., Mikami, B., and Esaki, N. (1999) J. Biochem. 126, 781-786] and only leads to formation of the isoxazole end product (the result of the transaminase pathway) in the case of d-cycloserine, in contrast to results obtained using the wild-type enzyme. l-Cycloserine, on the other hand, utilizes a number of alternative pathways in the absence of Y265, emphasizing the importance of Y265 in both the inactivation and racemization pathway. In combination with the kinetics of inactivation, these results suggest roles for each of the two catalytic bases in racemization and inactivation, as well as the importance of Y265 in "steering" the chemistry to favor one pathway over another.
Effect of a Y265F mutant on the transamination-based cycloserine inactivation of alanine racemase.,Fenn TD, Holyoak T, Stamper GF, Ringe D Biochemistry. 2005 Apr 12;44(14):5317-27. PMID:15807525[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, Holyoak T, Stamper GF, Ringe D. Effect of a Y265F mutant on the transamination-based cycloserine inactivation of alanine racemase. Biochemistry. 2005 Apr 12;44(14):5317-27. PMID:15807525 doi:10.1021/bi047842l
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