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| | <StructureSection load='4lut' size='340' side='right'caption='[[4lut]], [[Resolution|resolution]] 2.26Å' scene=''> | | <StructureSection load='4lut' size='340' side='right'caption='[[4lut]], [[Resolution|resolution]] 2.26Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lut]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LUT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lut]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LUT 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='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='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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4lut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lut OCA], [https://pdbe.org/4lut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lut RCSB], [https://www.ebi.ac.uk/pdbsum/4lut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lut ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alr2, CD630_34630 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272563 Clostridioides difficile 630])</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=4lut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lut OCA], [http://pdbe.org/4lut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lut RCSB], [http://www.ebi.ac.uk/pdbsum/4lut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lut ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q180W0_CLOD6 Q180W0_CLOD6]] Catalyzes the interconversion of L-alanine and D-alanine. May also act on other amino acids (By similarity).[HAMAP-Rule:MF_01201] | + | [https://www.uniprot.org/uniprot/Q180W0_CLOD6 Q180W0_CLOD6] Catalyzes the interconversion of L-alanine and D-alanine. May also act on other amino acids (By similarity).[HAMAP-Rule:MF_01201] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alanine racemase]] | |
| | [[Category: Clostridioides difficile 630]] | | [[Category: Clostridioides difficile 630]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Asojo, O A]] | + | [[Category: Asojo OA]] |
| - | [[Category: Isomerase-isomerase inhibitor complex]]
| + | |
| Structural highlights
Function
Q180W0_CLOD6 Catalyzes the interconversion of L-alanine and D-alanine. May also act on other amino acids (By similarity).[HAMAP-Rule:MF_01201]
Publication Abstract from PubMed
Clostridium difficile, a Gram-positive, spore-forming anaerobic bacterium, is the leading cause of infectious diarrhea among hospitalized patients. C. difficile is frequently associated with antibiotic treatment, and causes diseases ranging from antibiotic-associated diarrhea to life-threatening pseudomembranous colitis. The severity of C. difficile infections is exacerbated by the emergence of hypervirulent and multidrug-resistant strains, which are difficult to treat and are often associated with increased mortality rates. Alanine racemase (Alr) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the reversible racemization of L- and D-alanine. Since D-alanine is an essential component of the bacterial cell-wall peptidoglycan, and there are no known Alr homologs in humans, this enzyme is being tested as an antibiotic target. Cycloserine is an antibiotic that inhibits Alr. In this study, the catalytic properties and crystal structures of recombinant Alr from the virulent and multidrug-resistant C. difficile strain 630 are presented. Three crystal structures of C. difficile Alr (CdAlr), corresponding to the complex with PLP, the complex with cycloserine and a K271T mutant form of the enzyme with bound PLP, are presented. The structures are prototypical Alr homodimers with two active sites in which the cofactor PLP and cycloserine are localized. Kinetic analyses reveal that the K271T mutant CdAlr has the highest catalytic constants reported to date for any Alr. Additional studies are needed to identify the basis for the high catalytic activity. The structural and activity data presented are first steps towards using CdAlr for the development of structure-based therapeutics for C. difficile infections.
Structural and biochemical analyses of alanine racemase from the multidrug-resistant Clostridium difficile strain 630.,Asojo OA, Nelson SK, Mootien S, Lee Y, Rezende WC, Hyman DA, Matsumoto MM, Reiling S, Kelleher A, Ledizet M, Koski RA, Anthony KG Acta Crystallogr D Biol Crystallogr. 2014 Jul 1;70(Pt 7):1922-33. doi:, 10.1107/S1399004714009419. Epub 2014 Jun 29. PMID:25004969[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Asojo OA, Nelson SK, Mootien S, Lee Y, Rezende WC, Hyman DA, Matsumoto MM, Reiling S, Kelleher A, Ledizet M, Koski RA, Anthony KG. Structural and biochemical analyses of alanine racemase from the multidrug-resistant Clostridium difficile strain 630. Acta Crystallogr D Biol Crystallogr. 2014 Jul 1;70(Pt 7):1922-33. doi:, 10.1107/S1399004714009419. Epub 2014 Jun 29. PMID:25004969 doi:http://dx.doi.org/10.1107/S1399004714009419
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