Related Experiment Video
Updated: Jul 13, 2026
10:46
Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
Published on: May 3, 2017
Structural basis for glutamate racemase inhibition
Kook-Han Kim1, Young-Jong Bong, Joon Kyu Park
1Life Sciences Division, Korea Institute of Science and Technology, 39-1 Hawolkok-Dong, Sungbuk-Gu, Seoul, Korea.
Journal of Molecular Biology
|July 31, 2007
Summary
Structural insights into glutamate racemase (GluR) from Streptococcus pyogenes reveal its potential as a novel antibacterial drug target. Understanding inhibitor binding provides a basis for designing new antibiotics against bacterial infections.
Area of Science:
- Biochemistry
- Structural Biology
- Microbiology
Background:
- D-Glutamic acid is essential for bacterial peptidoglycan synthesis.
- Glutamate racemase (GluR) inter-converts D and L-glutamate, making it a key enzyme in this pathway.
- GluR is a promising target for developing new antibacterial agents.
Purpose of the Study:
- To determine the crystal structures of Streptococcus pyogenes GluR.
- To investigate the structural basis of inhibitor binding to GluR.
- To provide insights for the rational design of GluR inhibitors.
Main Methods:
- X-ray crystallography was used to obtain structures of GluR in inhibitor-free and inhibitor-bound forms.
- Crystallization yielded diffraction data to resolutions of 2.25 A and 2.5 A.
- Biophysical methods like gel filtration and dynamic light scattering were employed.
Main Results:
- The crystal structures revealed GluR comprises two pseudo-2-fold symmetric alpha/beta domains with the active site at the interface.
- A potent competitive inhibitor, gamma-2-naphthylmethyl-D-glutamate, binds via hydrogen bonds and hydrophobic interactions.
- Inhibitor binding induced conformational changes in an active site loop.
- GluR exists as a dimer in both crystal forms, with conserved dimer interface interactions.
Conclusions:
- The determined structures provide a detailed molecular understanding of GluR.
- The findings highlight GluR as a viable target for antibacterial drug development.
- Structural information can guide the design of more effective GluR-targeting antibiotics.
Related Concept Videos
01:14Antiepileptic Drugs: Glutamate Antagonists
Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
01:29Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
02:30Racemic Mixtures and the Resolution of Enantiomers
A racemic mixture, or racemate, is an equimolar mixture of enantiomers of a molecule that can be separated using their unique interaction with chiral molecules or media. Racemic mixtures are denoted by the (±)- prefix. This ‘optical rotation descriptor’ applies to the whole solution of a racemic mixture rather than a specific stereoisomer. Enantiomers typically have the same physical and chemical properties. Hence, they are not easily separable. However, enantiomers can exhibit different...