Molecule Information

General Information of the Molecule (ID: Mol04026)

• Name: Glutamate dehydrogenase 2 (GLUD2) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: GLUD2
• Gene ID: 2747
• Location: chrX:121047610-121050094[+]
• Sequence:
  MYRYLAKALLPSRAGPAALGSAANHSAALLGRGRGQPAAASQPGLALAARRHYSELVADR
  EDDPNFFKMVEGFFDRGASIVEDKLVKDLRTQESEEQKRNRVRGILRIIKPCNHVLSLSF
  PIRRDDGSWEVIEGYRAQHSQHRTPCKGGIRYSTDVSVDEVKALASLMTYKCAVVDVPFG
  GAKAGVKINPKNYTENELEKITRRFTMELAKKGFIGPGVDVPAPDMNTGEREMSWIADTY
  ASTIGHYDINAHACVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILGMTPGFR
  DKTFVVQGFGNVGLHSMRYLHRFGAKCIAVGESDGSIWNPDGIDPKELEDFKLQHGSILG
  FPKAKPYEGSILEVDCDILIPAATEKQLTKSNAPRVKAKIIAEGANGPTTPEADKIFLER
  NILVIPDLYLNAGGVTVSYFEWLKNLNHVSYGRLTFKYERDSNYHLLLSVQESLERKFGK
  HGGTIPIVPTAEFQDSISGASEKDIVHSALAYTMERSARQIMHTAMKYNLGLDLRTAAYV
  NAIEKVFKVYSEAGVTFT
• 3D-structure: PDB ID: 6G2U; Classification: Oxidoreductase; Method: X-ray diffraction; Resolution: 2.93 Å
• Function: Important for recycling the chief excitatory neurotransmitter, glutamate, during neurotransmission.
• Uniprot ID: DHE4_HUMAN
• Ensembl ID: ENSG00000182890
• HGNC ID: HGNC:4336

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Prednisolone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3] [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Resistant Drug: Prednisolone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SEM-K2 cells; Blood; Homo sapiens (Human); CVCL_S906
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

References

• Ref 1: Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Childhood Acute Lymphoblastic Leukaemia Cells. Int J Mol Sci. 2023 Feb 8;24(4):3378.