Crystal structure of a pyridoxal 5′‐phosphate‐dependent aspartate racemase derived from the bivalve mollusc Scapharca broughtonii

• Published in: Acta crystallographica. Section F, Structural biology communications Vol. 73; no. 12; pp. 651 - 656
• Main Authors: Mizobuchi, Taichi, Nonaka, Risako, Yoshimura, Motoki, Abe, Katsumasa, Takahashi, Shouji, Kera, Yoshio, Goto, Masaru
• Format: Journal Article
• Language: English
• Published: 5 Abbey Square, Chester, Cheshire CH1 2HU, England International Union of Crystallography 01.12.2017; Wiley Subscription Services, Inc
• Subjects: Amino Acid Isomerases - chemistry; Amino Acid Isomerases - genetics; Amino Acid Isomerases - metabolism; Animals; Aspartate racemase; Binding Sites; Biosynthesis; Bivalvia; Carboxyl group; Catalytic Domain; Crystal structure; Crystallography, X-Ray; Dehydration; Enzymes; In vivo methods and tests; Models, Molecular; Phosphates; Proline; Protein Conformation; pyridoxal 5′‐phosphate; Pyridoxal Phosphate - chemistry; Racemization; Research Communications; Scapharca - enzymology; Scapharca broughtonii; Serine; Serine racemase; Substrates; serine racemase; crystal structure; aspartate racemase; pyridoxal 5′-phosphate; Scapharca broughtonii
• ISSN: 2053-230X; 2053-230X
• DOI: 10.1107/S2053230X17015813

Aspartate racemase (AspR) is a pyridoxal 5′‐phosphate (PLP)‐dependent enzyme that is responsible for d‐aspartate biosynthesis in vivo. To the best of our knowledge, this is the first study to report an X‐ray crystal structure of a PLP‐dependent AspR, which was resolved at 1.90 Å resolution. The AspR derived from the bivalve mollusc Scapharca broughtonii (SbAspR) is a type II PLP‐dependent enzyme that is similar to serine racemase (SR) in that SbAspR catalyzes both racemization and dehydration. Structural comparison of SbAspR and SR shows a similar arrangement of the active‐site residues and nucleotide‐binding site, but a different orientation of the metal‐binding site. Superposition of the structures of SbAspR and of rat SR bound to the inhibitor malonate reveals that Arg140 recognizes the β‐carboxyl group of the substrate aspartate in SbAspR. It is hypothesized that the aromatic proline interaction between the domains, which favours the closed form of SbAspR, influences the arrangement of Arg140 at the active site. The crystal structure of a pyridoxal 5′‐phosphate‐dependent aspartate racemase derived from Scapharca broughtonii has been resolved at 1.90 Å resolution.