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| | ==Crystal structure of a thermostable alanine racemase from Thermoanaerobacter tengcongensis MB4== | | ==Crystal structure of a thermostable alanine racemase from Thermoanaerobacter tengcongensis MB4== |
| - | <StructureSection load='4y2w' size='340' side='right' caption='[[4y2w]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4y2w' size='340' side='right'caption='[[4y2w]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4y2w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cals4 Cals4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y2W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y2W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4y2w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Caldanaerobacter_subterraneus_subsp._tengcongensis_MB4 Caldanaerobacter subterraneus subsp. tengcongensis MB4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y2W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alr1, TTE1207 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273068 CALS4])</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=4y2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y2w OCA], [https://pdbe.org/4y2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y2w RCSB], [https://www.ebi.ac.uk/pdbsum/4y2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y2w 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=4y2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y2w OCA], [http://pdbe.org/4y2w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y2w RCSB], [http://www.ebi.ac.uk/pdbsum/4y2w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y2w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ALR1_CALS4 ALR1_CALS4]] Catalyzes the interconversion of L-alanine and D-alanine. May also act on other amino acids.[HAMAP-Rule:MF_01201] | + | [https://www.uniprot.org/uniprot/ALR1_CALS4 ALR1_CALS4] Catalyzes the interconversion of L-alanine and D-alanine. May also act on other amino acids.[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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| | ==See Also== | | ==See Also== |
| - | *[[Alanine racemase|Alanine racemase]] | + | *[[Alanine racemase 3D structures|Alanine racemase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alanine racemase]] | + | [[Category: Caldanaerobacter subterraneus subsp. tengcongensis MB4]] |
| - | [[Category: Cals4]] | + | [[Category: Large Structures]] |
| - | [[Category: Dong, H]] | + | [[Category: Dong H]] |
| - | [[Category: Ju, J]] | + | [[Category: Ju J]] |
| - | [[Category: Xu, X]] | + | [[Category: Xu X]] |
| - | [[Category: Gln360]]
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| - | [[Category: Isomerase]]
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| Structural highlights
Function
ALR1_CALS4 Catalyzes the interconversion of L-alanine and D-alanine. May also act on other amino acids.[HAMAP-Rule:MF_01201]
Publication Abstract from PubMed
Pyridoxal 5'-phosphate (PLP) dependent alanine racemase catalyzes racemization of L-Ala to D-Ala, a key component of the peptidoglycan network in bacterial cell wall. It has been extensively studied as an important antimicrobial drug target due to its restriction in eukaryotes. However, many marketed alanine racemase inhibitors also act on eukaryotic PLP-dependent enzymes and cause side effects. A thermostable alanine racemase (AlrTt) from Thermoanaerobacter tengcongensis MB4 contains an evolutionarily non-conserved residue Gln360 in inner layer of the substrate entryway, which is supposed to be a key determinant in substrate specificity. Here we determined the crystal structure of AlrTt in complex with L-Ala at 2.7 A resolution, and investigated the role of Gln360 by saturation mutagenesis and kinetic analysis. Compared to typical bacterial alanine racemase, presence of Gln360 and conformational changes of active site residues disrupted the hydrogen bonding interactions necessary for proper PLP immobilization, and decreased both the substrate affinity and turnover number of AlrTt. However, it could be complemented by introduction of hydrophobic amino acids at Gln360, through steric blocking and interactions with a hydrophobic patch near active site pocket. These observations explained the low racemase activity of AlrTt, revealed the essential role of Gln360 in substrate selection, and its preference for hydrophobic amino acids especially Tyr in bacterial alanine racemization. Our work will contribute new insights into the alanine racemization mechanism for antimicrobial drug development.
Crystal Structure of a Thermostable Alanine Racemase from Thermoanaerobacter tengcongensis MB4 Reveals the Role of Gln360 in Substrate Selection.,Sun X, He G, Wang X, Xu S, Ju J, Xu X PLoS One. 2015 Jul 28;10(7):e0133516. doi: 10.1371/journal.pone.0133516., eCollection 2015. PMID:26218070[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun X, He G, Wang X, Xu S, Ju J, Xu X. Crystal Structure of a Thermostable Alanine Racemase from Thermoanaerobacter tengcongensis MB4 Reveals the Role of Gln360 in Substrate Selection. PLoS One. 2015 Jul 28;10(7):e0133516. doi: 10.1371/journal.pone.0133516., eCollection 2015. PMID:26218070 doi:http://dx.doi.org/10.1371/journal.pone.0133516
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