Molecule Information

General Information of the Molecule (ID: Mol00973)

Name	Glutathione biosynthesis bifunctional protein GshAB (GSHAB ) ,Enterococcus faecalis
Synonyms	Gamma-GCS-GS; GCS-GS; Gamma-ECS; GCS; Gamma-glutamylcysteine synthetase; GSH synthetase; GS; GSH-S; GSHase; Glutathione synthase; gshF; EF_3089 Click to Show/Hide
Molecule Type	Protein
Gene Name	gshAB
Sequence	MNYRELMQKKNVRPYVLMARFGLEKENQRSTREGLLATTEHPTVFGNRSYHPYIQTDFSE TQLELITPVANSGTEMLRFLDAIHDVARRSIPEDEMLWPLSMPPQLPTKDEEIKIAKLDQ YDAVLYRRYLAKEYGKRKQMVSGIHFNFEYDQALIQQLYDEQSEVTDCKQFKTKVYMKVA RNFLRYRWLITYLFGASPVSEDRYFRVYDDQPQEPVRSIRNSTYGYRNHDNVKVSYASLE RYLEDIHRMVENGLLSEEKEFYAPVRLRGGKQMSDLPKTGIRYIELRNLDLNPFSRLGIV EDTVDFLHYFMLYLLWTDEKEEADEWVKTGDIFNEQVALGHPHETIKLIAEGDRIFSEMI DMLDALGIRKGKEVVGKYYQQLRNPQDTVSGKMWTIIQENSNSELGNIFGNQYQSMAFER PYQLAGFREMELSTQIFLFDAIQKGLEIEILDEQEQFLKLQHGEHIEYVKNANMTSKDNY VVPLIMENKTVTKKILSAAGFHVPGGEEFSSFIEAQEAHLRYANKAFVVKPKSTNYGLGI TIFKEGASLEDFTEALRIAFKEDTAVLIEEFLPGTEYRFFVLDNDVKAIMLRVPANVTGD GKHTVEELVAAKNSDPLRGTNHRAPLELIQLNDLEKLMLKEQGLTIYSVPEKEQIVYLRE NSNVSTGGDSIDMTDVIDDSYKQIAIEAVAALGAKICGIDLIIPDKDVKGTRDSLTYGII EANFNPAMHMHVYPYAGQGRRLTMDVLKLLYPEVVQ Click to Show/Hide
Function	Synthesizes glutathione from L-glutamate and L-cysteine via gamma-L-glutamyl-L-cysteine. Click to Show/Hide
Uniprot ID	GSHAB_ENTFA
*Click to Show/Hide the Complete Species Lineage*
Kingdom: N.A. Phylum: Firmicutes Class: Bacilli Order: Lactobacillales Family: Enterococcaceae Genus: Enterococcus Species: Enterococcus faecalis

Type(s) of Resistant Mechanism of This Molecule

DISM: Drug Inactivation by Structure Modification

MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s)

2 drug(s) in total

Click to Show/Hide the Full List of Drugs

Cisplatin

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Metabolic Reprogramming via Altered Pathways (MRAP)			Click to Show/Hide
Disease Class: Ovarian cancer [ICD-11: 2C73.0]				[1]
Metabolic Type	Glutamine metabolism
Resistant Disease	Ovarian cancer [ICD-11: 2C73.0]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	A2780 cells	Ovary	Homo sapiens (Human)	CVCL_0134
	A2780CIS cells	Ovary	Homo sapiens (Human)	CVCL_1942
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Thus, this study aimed to elucidate the underlying mechanisms by which ovarian cancer cells acquire CDDP resistance.

Daptomycin

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)		Click to Show/Hide
Disease Class: Bacterial infection [ICD-11: 1A00-1C4Z]			[2]
Resistant Disease	Bacterial infection [ICD-11: 1A00-1C4Z]		Disease Info
Resistant Drug	Daptomycin		Drug Info
Molecule Alteration	Missense mutation	p.E354K
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Enterococcus faecalis S613		699185
Experiment for Molecule Alteration	Whole genome sequence assay; Allelic frequency measurement assay
Experiment for Drug Resistance	Agar dilution method assay
Mechanism Description	As a glutathione synthase, GshF has previously been implicated in the oxidative stress response across multiple species. GshF is commonly found among mammalian pathogens and could have a role in mitigating DNA damage caused by general oxidative. stress.

References

Ref 1	Reprogramming of glutamine metabolism via glutamine synthetase silencing induces cisplatin resistance in A2780 ovarian cancer cells. BMC Cancer. 2021 Feb 17;21(1):174.
Ref 2	Adaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistance. Antimicrob Agents Chemother. 2013 Nov;57(11):5373-83. doi: 10.1128/AAC.01473-13. Epub 2013 Aug 19.