1XW6

1.9 angstrom resolution structure of human glutathione S-transferase M1A-1A complexed with glutathione

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Structure Motif: Primary M-CSA Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1xw6a1	All alpha proteins	GST C-terminal domain-like	GST C-terminal domain-like	Glutathione S-transferase (GST), C-terminal domain	Class mu GST	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1xw6a2	Alpha and beta proteins (a/b)	Thioredoxin fold	Thioredoxin-like	Glutathione S-transferase (GST), N-terminal domain	Class mu GST	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1xw6b1	All alpha proteins	GST C-terminal domain-like	GST C-terminal domain-like	Glutathione S-transferase (GST), C-terminal domain	Class mu GST	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1xw6b2	Alpha and beta proteins (a/b)	Thioredoxin fold	Thioredoxin-like	Glutathione S-transferase (GST), N-terminal domain	Class mu GST	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1xw6c1	All alpha proteins	GST C-terminal domain-like	GST C-terminal domain-like	Glutathione S-transferase (GST), C-terminal domain	Class mu GST	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1xw6c2	Alpha and beta proteins (a/b)	Thioredoxin fold	Thioredoxin-like	Glutathione S-transferase (GST), N-terminal domain	Class mu GST	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1xw6d1	All alpha proteins	GST C-terminal domain-like	GST C-terminal domain-like	Glutathione S-transferase (GST), C-terminal domain	Class mu GST	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1xw6d2	Alpha and beta proteins (a/b)	Thioredoxin fold	Thioredoxin-like	Glutathione S-transferase (GST), N-terminal domain	Class mu GST	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	GST_C_3	e1xw6A1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: GST_C_3	ECOD (1.6)
A	GST_N_5	e1xw6A2	A: a+b three layers	X: Thioredoxin-like	H: Thioredoxin-like (From Topology)	T: Thioredoxin-like	F: GST_N_5	ECOD (1.6)
B	GST_C_3	e1xw6B1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: GST_C_3	ECOD (1.6)
B	GST_N_5	e1xw6B2	A: a+b three layers	X: Thioredoxin-like	H: Thioredoxin-like (From Topology)	T: Thioredoxin-like	F: GST_N_5	ECOD (1.6)
C	GST_C_3	e1xw6C1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: GST_C_3	ECOD (1.6)
C	GST_N_5	e1xw6C2	A: a+b three layers	X: Thioredoxin-like	H: Thioredoxin-like (From Topology)	T: Thioredoxin-like	F: GST_N_5	ECOD (1.6)
D	GST_C_3	e1xw6D1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: GST_C_3	ECOD (1.6)
D	GST_N_5	e1xw6D2	A: a+b three layers	X: Thioredoxin-like	H: Thioredoxin-like (From Topology)	T: Thioredoxin-like	F: GST_N_5	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.30.10	Alpha Beta	3-Layer(aba) Sandwich	Glutaredoxin	Glutaredoxin	CATH (4.3.0)
A	1.20.1050.10	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (4.3.0)
B	3.40.30.10	Alpha Beta	3-Layer(aba) Sandwich	Glutaredoxin	Glutaredoxin	CATH (4.3.0)
B	1.20.1050.10	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (4.3.0)
C	3.40.30.10	Alpha Beta	3-Layer(aba) Sandwich	Glutaredoxin	Glutaredoxin	CATH (4.3.0)
C	1.20.1050.10	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (4.3.0)
D	3.40.30.10	Alpha Beta	3-Layer(aba) Sandwich	Glutaredoxin	Glutaredoxin	CATH (4.3.0)
D	1.20.1050.10	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00043	Glutathione S-transferase, C-terminal domain (GST_C)	Glutathione S-transferase, C-terminal domain	GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins ...	GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain [1]. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes [2].	Domain
A, B, C, D	PF02798	Glutathione S-transferase, N-terminal domain (GST_N)	Glutathione S-transferase, N-terminal domain	Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity a ...	Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognised); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognised). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Glutathione S-transferase Mu 1	identical protein binding protein binding binding protein homodimerization activity protein dimerization activity amide binding modified amino acid binding ion binding oligopeptide binding anion binding glutathione binding sulfur compound binding small molecule binding glutathione transferase activity identical protein binding protein binding binding protein homodimerization activity protein dimerization activity amide binding modified amino acid binding ion binding oligopeptide binding anion binding glutathione binding sulfur compound binding small molecule binding glutathione transferase activity transferase activity transferase activity, transferring alkyl or aryl (other than methyl) groups catalytic activity enzyme binding	cellular response to stimulus catabolic process response to stimulus cellular response to xenobiotic stimulus xenobiotic catabolic process xenobiotic metabolic process response to xenobiotic stimulus cellular response to chemical stimulus response to chemical metabolic process cellular process nitrobenzene metabolic process benzene-containing compound metabolic process fatty acid metabolic process cellular response to stimulus catabolic process response to stimulus cellular response to xenobiotic stimulus xenobiotic catabolic process xenobiotic metabolic process response to xenobiotic stimulus cellular response to chemical stimulus response to chemical metabolic process cellular process nitrobenzene metabolic process benzene-containing compound metabolic process fatty acid metabolic process long-chain fatty acid metabolic process monocarboxylic acid biosynthetic process oxoacid metabolic process small molecule biosynthetic process long-chain fatty acid biosynthetic process hepoxilin metabolic process carboxylic acid metabolic process lipid biosynthetic process primary metabolic process organic acid metabolic process organic acid biosynthetic process fatty acid biosynthetic process carboxylic acid biosynthetic process hepoxilin biosynthetic process biosynthetic process small molecule metabolic process monocarboxylic acid metabolic process lipid metabolic process sulfur compound biosynthetic process glutathione derivative biosynthetic process sulfur compound metabolic process glutathione derivative metabolic process prostaglandin metabolic process icosanoid metabolic process unsaturated fatty acid metabolic process prostanoid metabolic process cellular detoxification of nitrogen compound cellular detoxification detoxification response to nitrogen compound detoxification of nitrogen compound response to toxic substance cellular response to stress response to stress cellular response to toxic substance glutathione metabolic process modified amino acid metabolic process amide metabolic process	intercellular bridge cellular anatomical structure intracellular anatomical structure cytoplasm cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR004046	Glutathione S-transferase, C-terminal	Domain
A, B, C, D	IPR010987	Glutathione S-transferase, C-terminal-like	Domain
A, B, C, D	IPR004045	Glutathione S-transferase, N-terminal	Domain
A, B, C, D	IPR003081	Glutathione S-transferase, Mu class	Family
A, B, C, D	IPR050213	Glutathione S-transferase superfamily	Family
A, B, C, D	IPR036282	Glutathione S-transferase, C-terminal domain superfamily	Homologous Superfamily
A, B, C, D	IPR036249	Thioredoxin-like superfamily	Homologous Superfamily
A, B, C, D	IPR040079	Glutathione transferase family	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P09488	renal cell carcinoma squamous cell carcinoma chromophobe renal cell carcinoma colorectal cancer non-alcoholic fatty liver disease Parkinson disease Raynaud disease asthma leukemia Liver Cirrhosis, Experimental prostate cancer drug allergy liver cancer type 2 diabetes mellitus urticaria renal cell carcinoma squamous cell carcinoma chromophobe renal cell carcinoma colorectal cancer non-alcoholic fatty liver disease Parkinson disease Raynaud disease asthma leukemia Liver Cirrhosis, Experimental prostate cancer drug allergy liver cancer type 2 diabetes mellitus urticaria malignant mesothelioma collecting duct carcinoma papillary renal cell carcinoma amphetamine abuse sarcomatoid renal cell carcinoma atherosclerosis urinary bladder cancer mesothelioma depressive disorder alcohol withdrawal disease susceptibility schizophrenia autism benign mesothelioma cancer urinary bladder neoplasm maturity-onset diabetes of the young clear cell renal carcinoma colorectal carcinoma neurodegenerative disease drug-induced liver injury rosacea hepatocellular carcinoma skin disease bipolar disorder carpal tunnel syndrome liver neoplasm renal carcinoma arteriosclerosis disorder inherited disease susceptibility breast carcinoma lung benign neoplasm

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	Glutathione S-transferase class-μ M-CSA #867	Glutathione S-transferases (GSTs) are promiscuous enzymes that catalyze several reactions with various substrates. Their essential function is detoxification of xenobiotic compounds that are conjugated to glutathione (GSH) and then excreted; other functions, not associated with detoxification, include repair of macromolecules oxidised by reactive oxygen species, regeneration of S-thiolated proteins, and biosynthesis of physiologically important metabolites. There are two proposed mechanisms regarding GSH activation depending on the conformation of Tyr10 (in and out). Both appear to be viable where evidence supports both conformations.	Defined by 3 residues: TYR:A-7 [auth A-6]ARG:A-43 [auth A-42]HIS:A-108 [auth A-107] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 2.5.1.18 (PDB Primary Data) Search M-CSA Motif + EC 2.5.1.18

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.