9wrg

Amino acid racemase in complex with PLP-D-allo-Ile

spinqualitylabelsall models 9wrg, resolution 2.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9wrg is a 2 chain structure with sequence from Pyrococcus horikoshii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.68Å Ligands: ILP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed A broad substrate-specificity amino acid racemase (BAR; PH0138 gene product) exhibiting the activity toward ten amino acids and an alanine/serine-specific racemase (ASR; PH0782 gene product) were identified in the hyperthermophilic archaeon Pyrococcus horikoshii OT-3. Both enzymes were originally annotated as 4-aminobutyrate aminotransferase (GABA-AT) but were phylogenetically distinct from conventional GABA-ATs. In this study, we analyzed and compared the crystal structures of BAR and ASR. Crystal structures of BAR were determined in complex with N-(5'-phosphopyridoxyl)-l-isoleucine (PLP-l-Ile), N-(5'-phosphopyridoxyl)-d-allo-isoleucine (PLP-d-allo-Ile), and N-(5'-phosphopyridoxyl)-d-phenylalanine (PLP-d-Phe). On the other hand, crystal structures of ASR were determined in complex with N-(5'-phosphopyridoxyl)-l-alanine (PLP-l-Ala) and N-(5'-phosphopyridoxyl)-d-alanine (PLP-d-Ala). Structural comparisons of BAR revealed that the Phe35 and Trp463 side chains moved depending on the substrate, suggesting that the conformational flexibility of these side chains contributes to the broad substrate specificity of BAR. A structural comparison of BAR with ASR revealed that Trp456, Leu317*, and Met89* in ASR (the asterisk indicates a residue in the adjacent subunit) could sterically interfere with the side chain of d- or l-Phe, the preferred substrate of BAR. However, none of the ASR mutants tested (W456A, W456F, W456L, L317V, and M89T) showed detectable activity toward l-Phe. On the other hand, the L317V mutant of ASR exhibited altered substrate specificity toward linear amino acids, increasing the preference for l-2-aminobutyrate over l-Ala. In addition, substitutions at Trp456 in ASR severely reduced the activity toward l-Ala, suggesting that this residue is important for maintaining a productive substrate-binding geometry in ASR. Crystal structures of two different 4-aminobutyrate aminotransferase-like racemases from the hyperthermophilic archaeon Pyrococcus horikoshii.,Kawakami R, Nishimoto Y, Kawase T, Hayashi J, Yoneda K, Ohshima T, Sakuraba H Int J Biol Macromol. 2026 Mar;352:151119. doi: 10.1016/j.ijbiomac.2026.151119. , Epub 2026 Feb 25. PMID:41759851 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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