d-Aspartate, an Atypical Amino Acid with NMDA Receptor Agonist Features: Involvement in Schizophrenia

Errico, Francesco; Usiello, Alessandro

doi:10.1007/978-3-319-49795-2_5

Cited by 1 publication

(1 citation statement)

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“…Such a role is also proposed for L-aspartate (Cavallero et al, 2009), however this is still a matter of debate (Herring et al, 2015). Both stereoisomers bind to and activate N-methyl-D-aspartate receptors (NMDARs) (Patneau and Mayer, 1990) and might be involved in learning and memory processes (reviewed in Errico et al, 2018; Errico and Usiello, 2017; Katane and Homma, 2011; Ota et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Binding and transport of D-aspartate by the glutamate transporter homolog GltTk

Arkhipova

Trinco

Ettema

et al. 2019

eLife

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Mammalian glutamate transporters are crucial players in neuronal communication as they perform neurotransmitter reuptake from the synaptic cleft. Besides L-glutamate and L-aspartate, they also recognize D-aspartate, which might participate in mammalian neurotransmission and/or neuromodulation. Much of the mechanistic insight in glutamate transport comes from studies of the archeal homologs GltPh from Pyrococcus horikoshii and GltTk from Thermococcus kodakarensis. Here, we show that GltTk transports D-aspartate with identical Na+: substrate coupling stoichiometry as L-aspartate, and that the affinities (Kd and Km) for the two substrates are similar. We determined a crystal structure of GltTk with bound D-aspartate at 2.8 Å resolution. Comparison of the L- and D-aspartate bound GltTk structures revealed that D-aspartate is accommodated with only minor rearrangements in the structure of the binding site. The structure explains how the geometrically different molecules L- and D-aspartate are recognized and transported by the protein in the same way.

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