4y2w | pdb_00004y2w

Crystal structure of a thermostable alanine racemase from Thermoanaerobacter tengcongensis MB4

spinqualitylabelsall models 4y2w, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4y2w is a 2 chain structure with sequence from Caldanaerobacter subterraneus subsp. tengcongensis MB4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: ALA, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Alanine racemase 3D structures

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