Abstract
Aspartate racemases distribute and function to produce d-aspartate in eubacteria, archaea, invertebrates, and vertebrates. The aspartate racemases of eubacteria and hyperthermophilic archaea are pyridoxal 5′-phosphate (PLP) independent, and two conserved cysteine residues constitute the catalytic center. The crystal structure of the aspartate racemase of hyperthermophilic archaeon was determined. Based on this structure, the detailed reaction mechanism of the pyridoxal 5′-phosphate-independent aspartate racemase was studied by characterizing mutants and molecular dynamics simulations. However, it is still unclear how the catalytic cysteine residue can abstract a proton from the α-carbon. The aspartate in hyperthermophilic archaea is highly racemized, but the physiological role of aspartate racemase and d-aspartate in hyperthermophilic archaea is unknown. The aspartate racemases in invertebrates and vertebrates are PLP dependent. The aspartate racemases from invertebrates, bivalves, and Aplysia californica are homologous to serine racemases, but it has taken many years to identify the aspartate racemase responsible for the synthesis of d-Asp in mammals due to the lack of other amino acid racemases. The gene for the mammalian aspartate racemase was obtained via its homology with glutamate-oxaloacetate transaminase. Further studies on aspartate racemase will promote research on the mysterious functions of d-Asp in various organisms.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abe K, Takahashi S, Muroki Y, Kera Y, Yamada RH (2006) Cloning and expression of the pyridoxal 5′-phosphate-dependent aspartate racemase gene from the bivalve mollusk Scapharca broughtonii and characterization of the recombinant enzyme. J Biochem 139(2):235–244. doi:10.1093/jb/mvj028
Johnston MM, Diven WF (1969) Studies on amino acid racemases. I. Partial purification and properties of the alanine racemase from Lactobacillus fermenti. J Biol Chem 244(19):5414–5420
Kim PM, Duan X, Huang AS, Liu CY, Ming GL, Song H, Snyder SH (2010) Aspartate racemase, generating neuronal d-aspartate, regulates adult neurogenesis. Proc Natl Acad Sci U S A 107(7):3175–3179. doi:10.1073/pnas.0914706107
Lamont HC, Staudenbauer WL, Strominger JL (1972) Partial purification and characterization of an aspartate racemase from Streptococcus faecalis. J Biol Chem 247(16):5103–5106
Liu L, Iwata K, Kita A, Kawarabayasi Y, Yohda M, Miki K (2002a) Crystal structure of aspartate racemase from Pyrococcus horikoshii OT3 and its implications for molecular mechanism of PLP-independent racemization. J Mol Biol 319(2):479–489. doi:10.1016/s0022-2836(02)00296-6
Liu L, Iwata K, Yohda M, Miki K (2002b) Structural insight into gene duplication, gene fusion and domain swapping in the evolution of PLP-independent amino acid racemases. FEBS Lett 528(1–3):114–118
Long Z, Lee JA, Okamoto T, Sekine M, Nimura N, Imai K, Yohda M, Maruyama T, Sumi M, Kamo N, Yamagishi A, Oshima T, Homma H (2001) Occurrence of d-amino acids and a pyridoxal 5′-phosphate-dependent aspartate racemase in the acidothermophilic archaeon, Thermoplasma acidophilum. Biochem Biophys Res Commun 281(2):317–321. doi:10.1006/bbrc.2001.4353
Matsumoto M, Homma H, Long Z, Imai K, Iida T, Maruyama T, Aikawa Y, Endo I, Yohda M (1999) Occurrence of free d-amino acids and aspartate racemases in hyperthermophilic archaea. J Bacteriol 181(20):6560–6563
Nagata Y, Fujiwara T, Kawaguchi-Nagata K, Fukumori Y, Yamanaka T (1998) Occurrence of peptidyl d-amino acids in soluble fractions of several eubacteria, archaea and eukaryotes. Biochim Biophys Acta 1379(1):76–82
Ohtaki A, Nakano Y, Iizuka R, Arakawa T, Yamada K, Odaka M, Yohda M (2008) Structure of aspartate racemase complexed with a dual substrate analogue, citric acid, and implications for the reaction mechanism. Proteins 70(4):1167–1174. doi:10.1002/prot.21528
Okada H, Yohda M, Giga-Hama Y, Ueno Y, Ohdo S, Kumagai H (1991) Distribution and purification of aspartate racemase in lactic acid bacteria. Biochim Biophys Acta 1078(3):377–382
Shibata K, Watanabe T, Yoshikawa H, Abe K, Takahashi S, Kera Y, Yamada R-h (2003a) Nucleotides modulate the activity of aspartate racemase of Scapharca broughtonii. Comp Biochem Physiol B Biochem Mol Biol 134(4):713–719. doi:10.1016/s1096-4959(03)00031-9
Shibata K, Watanabe T, Yoshikawa H, Abe K, Takahashi S, Kera Y, Yamada RH (2003b) Purification and characterization of aspartate racemase from the bivalve mollusk Scapharca broughtonii. Comp Biochem Physiol B Biochem Mol Biol 134(2):307–314
Staudenbauer W, Strominger JL (1972) Activation of d-aspartic acid for incorporation into peptidoglycan. J Biol Chem 247(16):5095–5102
Wang L, Ota N, Romanova EV, Sweedler JV (2011) A novel pyridoxal 5′-phosphate-dependent amino acid racemase in the Aplysia californica central nervous system. J Biol Chem 286(15):13765–13774. doi:10.1074/jbc.M110.178228
Yamada RH, Kera Y, Takahashi S (2006) Occurrence and functions of free d-aspartate and its metabolizing enzymes. Chem Rec 6(5):259–266. doi:10.1002/tcr.20089
Yamauchi T, Choi SY, Okada H, Yohda M, Kumagai H, Esaki N, Soda K (1992) Properties of aspartate racemase, a pyridoxal 5′-phosphate-independent amino acid racemase. J Biol Chem 267(26):18361–18364
Yohda M, Okada H, Kumagai H (1991) Molecular cloning and nucleotide sequencing of the aspartate racemase gene from lactic acid bacteria Streptococcus thermophilus. Biochim Biophys Acta 1089(2):234–240
Yohda M, Endo I, Abe Y, Ohta T, Iida T, Maruyama T, Kagawa Y (1996) Gene for aspartate racemase from the sulfur-dependent hyperthermophilic archaeum, Desulfurococcus strain SY. J Biol Chem 271(36):22017–22021
Yoshida T, Seko T, Okada O, Iwata K, Liu L, Miki K, Yohda M (2006) Roles of conserved basic amino acid residues and activation mechanism of the hyperthermophilic aspartate racemase at high temperature. Proteins 64(2):502–512. doi:10.1002/prot.21010
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Japan
About this chapter
Cite this chapter
Yohda, M. (2016). Aspartate Racemase: Function, Structure, and Reaction Mechanism. In: Yoshimura, T., Nishikawa, T., Homma, H. (eds) D-Amino Acids. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56077-7_21
Download citation
DOI: https://doi.org/10.1007/978-4-431-56077-7_21
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-56075-3
Online ISBN: 978-4-431-56077-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)