Glutathione S-transferase P

Basic Information
Short Name	GSTP1-1, GST class-pi
UNP ID	P09211
Organism	Homo sapiens
Cys Site	Cys15, Cys48, Cys102
Family/Domain	Glutathione S-transferase, N-terminal domain, Glutathione S-transferase, C-terminal domain, GST superfamily, Pi family
Known Ligand	Ligand list
Function Type	Metabolic enzyme

Summary

Protein Function

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration. (From Uniprot)
Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based on their biochemical, immunologic, and structural properties, the soluble GSTs are categorized into 4 main classes: alpha, mu, pi, and theta.
The glutathione S-transferase pi gene (GSTP1) is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are thought to function in xenobiotic metabolism and play a role in susceptibility to cancer, and other diseases. (From Wikipedia)

Cys Function & Property

Cys15 and Cys48 are very close to the binding site of Glutathione.

• Hydrophobic property:

• SASA：

Cys15: 0 A^2

Cys48: 5.892 A^2

Cys102: 50.785 A^2

Protein Sequence

MPPYTVVYFP VRGRCAALRM LLADQGQSWK EEVVTVETWQ EGSLKASCLY
GQLPKFQDGD LTLYQSNTIL RHLGRTLGLY GKDQQEAALV DMVNDGVEDL
RCKYISLIYT NYEAGKDDYV KALPGQLKPF ETLLSQNQGG KTFIVGDQIS
FADYNLLDLL LIHEVLAPGC LDAFPLLSAY VGRLSARPKL KAFLASPEYV
NLPINGNGKQ

Structural Information

• Known structures with covalent ligands:
  

Unknown

• Protein structure:

Related Pathway

• Glutathione metabolism
  
• Metabolism of xenobiotics by cytochrome P450
  
• Drug metabolism - cytochrome P450
  
• Drug metabolism - other enzymes
  
• Metabolic pathways
  
• Platinum drug resistance
  
• Pathways in cancer
  
• Chemical carcinogenesis
  
• Prostate cancer
  
• Hepatocellular carcinoma
  
• Fluid shear stress and atherosclerosis
  

Experimental Evidence

Cys Modification Assay, LC-MS/MS, Tryptic Digest, Back-titration Experiment, Isothermal Titration Calorimetry, Cys-directed Mutation

Reference

1. van Iersel M L P S, Ploemen J P H T M, Bello M L, et al. Interactions of α, β-unsaturated aldehydes and ketones with human glutathione S-transferase P1-1[J]. Chemico-biological interactions, 1997, 108(1-2): 67-78. 9463521
   
2. Boerma J S, Dragovic S, Vermeulen N P E, et al. Mass spectrometric characterization of protein adducts of multiple P450-dependent reactive intermediates of diclofenac to human glutathione-S-transferase P1-1[J]. Chemical research in toxicology, 2012, 25(11): 2532-2541. 22998212
   
3. Meng X, Howarth A, Earnshaw C J, et al. Detection of drug bioactivation in vivo: mechanism of nevirapine–albumin conjugate formation in patients[J]. Chemical research in toxicology, 2013, 26(4): 575-583. 23448204
   
4. Quesada‐Soriano I, Parker L J, Primavera A, et al. Diuretic drug binding to human glutathione transferase P1‐1: potential role of Cys‐101 revealed in the double mutant C47S/Y108V[J]. Journal of Molecular Recognition, 2011, 24(2): 220-234. 20540076
   
5. Callan H E, Jenkins R E, Maggs J L, et al. Multiple adduction reactions of nitroso sulfamethoxazole with cysteinyl residues of peptides and proteins: implications for hapten formation[J]. Chemical research in toxicology, 2009, 22(5): 937-948. 19358516