PDBsum entry 20gs

Transferase

PDB id: 20gs

Contents

Protein chain

208 a.a. *

Ligands

MES ×2

CBD ×2

Waters ×101

* Residue conservation analysis

PDB id:

20gs

Name:

Transferase

Title:

Glutathione s-transferase p1-1 complexed with cibacron blue

Structure:

Glutathione s-transferase. Chain: a, b. Synonym: gstp1-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: ubiquitous. Tissue: ubiquitous. Cell: ubiquitous. Cellular_location: cytosol. Gene: gstp1. Expressed in: escherichia coli.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.45Å R-factor: 0.229 R-free: 0.280

Authors:

A.J.Oakley,M.Lo Bello,M.Nuccetelli,A.P.Mazzetti,M.W.Parker

Key ref:

A.J.Oakley et al. (1999). The ligandin (non-substrate) binding site of human Pi class glutathione transferase is located in the electrophile binding site (H-site). J Mol Biol, 291, 913-926. PubMed id: 10452896 DOI: 10.1006/jmbi.1999.3029

Date:

16-Dec-97 Release date: 30-Dec-98

Protein chains

P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P from Homo sapiens

Seq: 210 a.a.

Struc: 208 a.a.

Enzyme reactions

• Enzyme class: E.C.2.5.1.18 - glutathione transferase.
• Reaction: RX + glutathione = an S-substituted glutathione + a halide anion + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1006/jmbi.1999.3029

J Mol Biol 291:913-926 (1999)

PubMed id: 10452896

The ligandin (non-substrate) binding site of human Pi class glutathione transferase is located in the electrophile binding site (H-site).

A.J.Oakley, M.Lo Bello, M.Nuccetelli, A.P.Mazzetti, M.W.Parker.

ABSTRACT

Glutathione S -transferases (GSTs) play a pivotal role in the detoxification of foreign chemicals and toxic metabolites. They were originally termed ligandins because of their ability to bind large molecules (molecular masses >400 Da), possibly for storage and transport roles. The location of the ligandin site in mammalian GSTs is still uncertain despite numerous studies in recent years. Here we show by X-ray crystallography that the ligandin binding site in human pi class GST P1-1 occupies part of one of the substrate binding sites. This work has been extended to the determination of a number of enzyme complex crystal structures which show that very large ligands are readily accommodated into this substrate binding site and in all, but one case, causes no significant movement of protein side-chains. Some of these molecules make use of a hitherto undescribed binding site located in a surface pocket of the enzyme. This site is conserved in most, but not all, classes of GSTs suggesting it may play an important functional role.

Selected figure(s)

Figure 1.
Figure 1. Schematic representation of the inhibitors. (a) Sulfasalazine. The numbering scheme is taken from [van der Sluis and Spek 1990]. (b) S-Nonyl GSH; (c) Cibacron blue; (d) bromosulfophthalein; (e) 2,4-dinitrophenyl GSH.

Figure 3.
Figure 3. A comparison of the binding locations of GSH conjugates derived from the various crystal structures of pi class GSTs presented here. The superposition was based on overlaying the coordinates of the respective N-terminal domains. The ligands are overlayed on a schematic of the N-terminal domain of the human pi class enzyme. (a) Stereo view showing all inhibitors described in the text. The inhibitors are coloured as follows: SLZ, yellow;S-nonyl GSH, cyan; CB, dark blue; BS no.1, red; BS no. 2, magenta; DNP GSH, green. The side-chains of Phe8 and Tyr108 are shown. (b) Comparison of the binding locations of DNP GSH (denoted by yellow bonds) and BS no. 1 (denoted by red bonds). These pictures were generated with the program MOLSCRIPT [Kraulis 1991].

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 291, 913-926) copyright 1999.

Figures were selected by the author.